Joseph Santos-Sacchi

Summary

Affiliation: Yale University
Country: USA

Publications

  1. pmc Chloride Anions Regulate Kinetics but Not Voltage-Sensor Qmax of the Solute Carrier SLC26a5
    Joseph Santos-Sacchi
    Department of Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut Electronic address
    Biophys J 110:2551-61. 2016
  2. pmc Chloride-driven electromechanical phase lags at acoustic frequencies are generated by SLC26a5, the outer hair cell motor protein
    Joseph Santos-Sacchi
    Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut Neurobiology, Yale University School of Medicine, New Haven, Connecticut Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut Electronic address
    Biophys J 107:126-33. 2014
  3. pmc Mapping the distribution of outer hair cell voltage-dependent conductances by electrical amputation
    J Santos-Sacchi
    Section of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Biophys J 73:1424-9. 1997
  4. doi request reprint Cochlear mechanics: no shout but a twist in the absence of prestin
    Joseph Santos-Sacchi
    Department of Surgery, Otolaryngology, Cellular and Molecular Physiology, and Neurobiology, Yale University School of Medicine, BML 244, 333 Cedar Street, New Haven, Connecticut 06510, USA
    Curr Biol 18:R304-6. 2008
  5. ncbi request reprint Control of mammalian cochlear amplification by chloride anions
    Joseph Santos-Sacchi
    Section of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Neurosci 26:3992-8. 2006
  6. ncbi request reprint On the temperature and tension dependence of the outer hair cell lateral membrane conductance GmetL and its relation to prestin
    Joseph Santos-Sacchi
    Department of Otolaryngology, Yale University School of Medicine, BML 246, 333 Cedar Street, New Haven, CT 06510, USA
    Pflugers Arch 452:283-9. 2006
  7. pmc Determination of cell capacitance using the exact empirical solution of partial differential Y/partial differential Cm and its phase angle
    Joseph Santos-Sacchi
    Otolaryngology and Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Biophys J 87:714-27. 2004
  8. ncbi request reprint New tunes from Corti's organ: the outer hair cell boogie rules
    Joseph Santos-Sacchi
    Yale University School of Medicine, Otolaryngology and Neurobiology, BML 244 333 Cedar Street, New Haven, CT 06510, USA
    Curr Opin Neurobiol 13:459-68. 2003
  9. ncbi request reprint Excitation of fluorescent dyes inactivates the outer hair cell integral membrane motor protein prestin and betrays its lateral mobility
    Joseph Santos-Sacchi
    Surgery Otolaryngology and Neurobiology, BML 244, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
    Pflugers Arch 446:617-22. 2003
  10. ncbi request reprint Functional motor microdomains of the outer hair cell lateral membrane
    Joseph Santos-Sacchi
    Department of Surgery Otolaryngology and Section of Neurobiology, BML 244, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510, USA
    Pflugers Arch 445:331-6. 2002

Collaborators

Detail Information

Publications42

  1. pmc Chloride Anions Regulate Kinetics but Not Voltage-Sensor Qmax of the Solute Carrier SLC26a5
    Joseph Santos-Sacchi
    Department of Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut Electronic address
    Biophys J 110:2551-61. 2016
    ....
  2. pmc Chloride-driven electromechanical phase lags at acoustic frequencies are generated by SLC26a5, the outer hair cell motor protein
    Joseph Santos-Sacchi
    Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut Neurobiology, Yale University School of Medicine, New Haven, Connecticut Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut Electronic address
    Biophys J 107:126-33. 2014
    ..These lags may contribute to canceling viscous drag, a requirement for many models of cochlear amplification. ..
  3. pmc Mapping the distribution of outer hair cell voltage-dependent conductances by electrical amputation
    J Santos-Sacchi
    Section of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Biophys J 73:1424-9. 1997
    ....
  4. doi request reprint Cochlear mechanics: no shout but a twist in the absence of prestin
    Joseph Santos-Sacchi
    Department of Surgery, Otolaryngology, Cellular and Molecular Physiology, and Neurobiology, Yale University School of Medicine, BML 244, 333 Cedar Street, New Haven, Connecticut 06510, USA
    Curr Biol 18:R304-6. 2008
    ..Recent evidence indicates that the molecular motor that drives this amplification, prestin, may do more than boogie...
  5. ncbi request reprint Control of mammalian cochlear amplification by chloride anions
    Joseph Santos-Sacchi
    Section of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Neurosci 26:3992-8. 2006
    ....
  6. ncbi request reprint On the temperature and tension dependence of the outer hair cell lateral membrane conductance GmetL and its relation to prestin
    Joseph Santos-Sacchi
    Department of Otolaryngology, Yale University School of Medicine, BML 246, 333 Cedar Street, New Haven, CT 06510, USA
    Pflugers Arch 452:283-9. 2006
    ..The dissociation of SLC26A5 (prestin) and GmetL theoretically provides for a modifiable anionic feedback to prestin via the degree of spatial separation between these interacting partners within the OHC lateral membrane...
  7. pmc Determination of cell capacitance using the exact empirical solution of partial differential Y/partial differential Cm and its phase angle
    Joseph Santos-Sacchi
    Otolaryngology and Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Biophys J 87:714-27. 2004
    ..Finally, I provide simulation examples and physiological examples of how the method can be used to study processes that are routinely interrogated by measures of membrane capacitance...
  8. ncbi request reprint New tunes from Corti's organ: the outer hair cell boogie rules
    Joseph Santos-Sacchi
    Yale University School of Medicine, Otolaryngology and Neurobiology, BML 244 333 Cedar Street, New Haven, CT 06510, USA
    Curr Opin Neurobiol 13:459-68. 2003
    ..A review of this remarkable progress is attempted...
  9. ncbi request reprint Excitation of fluorescent dyes inactivates the outer hair cell integral membrane motor protein prestin and betrays its lateral mobility
    Joseph Santos-Sacchi
    Surgery Otolaryngology and Neurobiology, BML 244, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
    Pflugers Arch 446:617-22. 2003
    ..These data indicate that lateral diffusion of prestin occurs within the cell's lateral plasma membrane...
  10. ncbi request reprint Functional motor microdomains of the outer hair cell lateral membrane
    Joseph Santos-Sacchi
    Department of Surgery Otolaryngology and Section of Neurobiology, BML 244, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510, USA
    Pflugers Arch 445:331-6. 2002
    ..These data highlight the functional independence of microdomains and imply that measured whole cell characteristics may differ from the microscopic characteristics of elementary motors...
  11. ncbi request reprint Temperature dependence of outer hair cell nonlinear capacitance
    J Santos-Sacchi
    Section of Otolaryngology, Yale University School of Medicine, New Haven, CT 06510, USA
    Hear Res 116:99-106. 1998
    ..Such temperature-dependent effects on the OHC may mediate known temperature effects on in vivo cochlear physiology...
  12. pmc Effects of membrane potential on the voltage dependence of motility-related charge in outer hair cells of the guinea-pig
    J Santos-Sacchi
    Sections of Otolaryngology and Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    J Physiol 510:225-35. 1998
    ..Through modelling, we indicate how the effect may be explained by an intrinsic voltage-induced tension generated by the molecular motors residing in the lateral membrane...
  13. ncbi request reprint Density of motility-related charge in the outer hair cell of the guinea pig is inversely related to best frequency
    J Santos-Sacchi
    Section of Otolaryngology and Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Neurosci Lett 256:155-8. 1998
    ..This conservation of energy delivery is likely crucial for the function of the cochlear amplifier at high frequencies...
  14. ncbi request reprint Cell coupling in Corti's organ
    J Santos-Sacchi
    Surgery Otolaryngology and Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Brain Res Brain Res Rev 32:167-71. 2000
    ..In this review, data on both electrical and mechanical coupling are covered. While electrical coupling likely contributes to homeostasis in the organ, this concept is far from proven...
  15. pmc Effects of membrane potential and tension on prestin, the outer hair cell lateral membrane motor protein
    J Santos-Sacchi
    Sections of Otolaryngology and Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    J Physiol 531:661-6. 2001
    ..It remains possible that some other interacting molecular species within the lateral plasma membrane of the native OHC amplifies the effect of tension and prior voltage on prestin's activity...
  16. ncbi request reprint Furosemide alters nonlinear capacitance in isolated outer hair cells
    J Santos-Sacchi
    Section of Otolaryngology, Department of Surgery Otolaryngology, BML 244, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510, USA
    Hear Res 159:69-73. 2001
    ....
  17. ncbi request reprint Voltage-dependent changes in specific membrane capacitance caused by prestin, the outer hair cell lateral membrane motor
    Joseph Santos-Sacchi
    Section of Otolaryngology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510 USA
    Pflugers Arch 444:99-106. 2002
    ..Thus, we conclude that a conformational change in the lateral membrane motor, prestin, additionally alters the dielectric constant and/or thickness of the lateral plasma membrane...
  18. pmc Fast electromechanical amplification in the lateral membrane of the outer hair cell
    Joseph Santos-Sacchi
    Department of Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Biophys J 96:739-47. 2009
    ..As with the forward transducer, the speed of the reverse transducer amplificatory event consequently impacts on high frequency peripheral auditory processing...
  19. pmc N-terminal-mediated homomultimerization of prestin, the outer hair cell motor protein
    Dhasakumar Navaratnam
    Departments of Neurology and Neurobiology, and Otolaryngology and Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
    Biophys J 89:3345-52. 2005
    ..These domains, which we have perturbed, likely contribute to allosteric modulation of prestin via interactions among prestin molecules or possibly between prestin and other proteins, as well...
  20. pmc Prestin surface expression and activity are augmented by interaction with MAP1S, a microtubule-associated protein
    Jun Ping Bai
    Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA
    J Biol Chem 285:20834-43. 2010
    ..These data highlight the importance of protein partner effects on prestin...
  21. pmc Conformational state-dependent anion binding in prestin: evidence for allosteric modulation
    Lei Song
    Department of Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut, USA
    Biophys J 98:371-6. 2010
    ..Furthermore, we hypothesize that prestin's susceptibility to many biophysical forces, and notably its piezoelectric nature, may reflect anion interactions with the motor...
  22. pmc Combinatorial cysteine mutagenesis reveals a critical intramonomer role for cysteines in prestin voltage sensing
    Jun Ping Bai
    Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA
    Biophys J 99:85-94. 2010
    ..Taken together, we believe these data indicate that intramembranous cysteines are constrained, possibly via disulfide bond formation, to ensure structural features of prestin required for normal voltage sensing and mechanical activity...
  23. pmc Prestin's anion transport and voltage-sensing capabilities are independent
    Jun Ping Bai
    Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA
    Biophys J 96:3179-86. 2009
    ..Finally, we distinguish 12 charged residues out of 22, residing within prestin's transmembrane regions, that contribute to unitary charge movement, i.e., voltage sensing. These data redefine our mechanistic concept of prestin...
  24. pmc Cl- flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig
    Volodymyr Rybalchenko
    Department of Surgery Otolaryngology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
    J Physiol 547:873-91. 2003
    ....
  25. pmc Disparities in voltage-sensor charge and electromotility imply slow chloride-driven state transitions in the solute carrier SLC26a5
    Lei Song
    Department of Surgery Otolaryngology, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 110:3883-8. 2013
    ..Such phase lags may help to effectively inject energy at the appropriate moment to enhance basilar membrane motion...
  26. pmc A highly expressing Tet-inducible cell line recapitulates in situ developmental changes in prestin's Boltzmann characteristics and reveals early maturational events
    Shumin Bian
    Department of Neurology, Yale School of Medicine, New Haven, CT 06520, USA
    Am J Physiol Cell Physiol 299:C828-35. 2010
    ..Finally, there is a gradual depolarizing shift in the voltage of peak capacitance, similar to that observed in developing OHCs. This inducible system offers many opportunities for detailed studies of prestin...
  27. pmc Real time measures of prestin charge and fluorescence during plasma membrane trafficking reveal sub-tetrameric activity
    Shumin Bian
    Department of Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut, United States of America
    PLoS ONE 8:e66078. 2013
    ..Thus, in agreement with previous observations we find that functional prestin is not an obligate tetramer...
  28. pmc Extracellular chloride regulation of Kv2.1, contributor to the major outward Kv current in mammalian outer hair cells
    Xiantao Li
    Department of Surgery Otolaryngology, YaleUniversity School of Medicine, New Haven, Connecticut 06511, USA
    Am J Physiol Cell Physiol 302:C296-306. 2012
    ..The Cl(-) sensitivity of Kv2.1 and its robust expression within OHCs verified by single-cell RT-PCR indicate that these channels underlie the OHC's extracellular Cl(-) sensitivity...
  29. ncbi request reprint En block C-terminal charge cluster reversals in prestin (SLC26A5): effects on voltage-dependent electromechanical activity
    Jun Ping Bai
    Neurology and Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Neurosci Lett 404:270-5. 2006
    ....
  30. pmc Patch-clamp recordings from lateral line neuromast hair cells of the living zebrafish
    Anthony J Ricci
    Department of Otolaryngology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Neurosci 33:3131-4. 2013
    ..Such capabilities will allow more detailed understanding of mechano-sensation of the zebrafish...
  31. pmc IR laser-induced perturbations of the voltage-dependent solute carrier protein SLC26a5
    Oluwarotimi Okunade
    Department of Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut
    Biophys J 105:1822-8. 2013
    ..This likely arises from prestin's unique ability to move sensor charge at kilohertz rates, which is required for the outer hair cells' role as a cochlear amplifier...
  32. pmc Gene expression gradients along the tonotopic axis of the chicken auditory epithelium
    Corey S Frucht
    Medical Scientist Training Program, Yale School of Medicine, New Haven, CT, USA
    J Assoc Res Otolaryngol 12:423-35. 2011
    ..Taken together, these results suggest mechanisms of induction and maintenance of tonotopicity and enhance our understanding of the complex nature of proximal-distal gene expression gradients in the chicken BP...
  33. pmc On membrane motor activity and chloride flux in the outer hair cell: lessons learned from the environmental toxin tributyltin
    Lei Song
    Otolaryngology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510, USA
    Biophys J 88:2350-62. 2005
    ..Notably, this observation identifies a new environmental threat for marine mammals by TBT, which is known to accumulate in the food chain...
  34. pmc Anion control of voltage sensing by the motor protein prestin in outer hair cells
    Volodymyr Rybalchenko
    Department of Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Biophys J 95:4439-47. 2008
    ..We find that the nature of the anion, including species, valence, and structure, regulates characteristics of the charge movement, signifying that anions play a more complicated role than simple voltage sensing in cochlear amplification...
  35. pmc Gene expression analysis of forskolin treated basilar papillae identifies microRNA181a as a mediator of proliferation
    Corey S Frucht
    Medical Scientist Training Program, Yale School of Medicine, New Haven, Connecticut, United States of America
    PLoS ONE 5:e11502. 2010
    ....
  36. doi request reprint Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels
    Caixia Lv
    Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520 8066, USA
    Cell Rep 15:2784-95. 2016
    ..Our results suggest that Ribeye makes up most of the synaptic ribbon density in neuromast hair cells and is necessary for proper localization of calcium channels and synaptic ribbons. ..
  37. pmc MicroRNA181a plays a key role in hair cell regeneration in the avian auditory epithelium
    Corey S Frucht
    Medical Scientist Training Program, Yale School of Medicine, 367 Cedar Street, Room 316 ESH, New Haven, CT 06522, USA
    Neurosci Lett 493:44-8. 2011
    ..MiR181a downregulation therefore seems to dimish the proliferative component of hair cell regeneration rather than prevent hair cell death following ototoxic injury...
  38. pmc Calcium-dependent synaptic vesicle trafficking underlies indefatigable release at the hair cell afferent fiber synapse
    Michael E Schnee
    Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA 94304, USA
    Neuron 70:326-38. 2011
    ..These data, supported by a mass action model, suggest sustained release at hair cell afferent fiber synapse is dictated by Ca(2+)-dependent vesicle recruitment from a reserve pool...
  39. doi request reprint A Walkthrough of Nonlinear Capacitance Measurement of Outer Hair Cells
    Lei Song
    Department of Surgery, Yale University School of Medicine, 208062, New Haven, CT, 06510, USA
    Methods Mol Biol 1427:501-12. 2016
    ..We use the software jClamp since it is tailored to capacitance measurement. Here we detail steps that we use to measure NLC. The walk through includes isolation of guinea pig OHCs, building voltage commands, recording, and analysis. ..
  40. pmc An electrical inspection of the subsurface cisternae of the outer hair cell
    Lei Song
    Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut
    Biophys J 108:568-77. 2015
    ..Finally, a cable model of the OHC, which can match our data, indicates that the SSC poses a minimal barrier to current flow across it, thereby facilitating rapid delivery of voltage excitation to the prestin-embedded lateral membrane...
  41. pmc A genetically-encoded YFP sensor with enhanced chloride sensitivity, photostability and reduced ph interference demonstrates augmented transmembrane chloride movement by gerbil prestin (SLC26a5)
    Sheng Zhong
    Dept of Surgery Otolaryngology, Yale University School of Medicine, New Haven, Connecticut, United States of America
    PLoS ONE 9:e99095. 2014
    ..Dynamic and accurate measurement of physiological concentrations of chloride would significantly affect our ability to study effects of chloride on cellular events...
  42. pmc Mitochondrial stress engages E2F1 apoptotic signaling to cause deafness
    Nuno Raimundo
    Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
    Cell 148:716-26. 2012
    ....