This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the mammalian vestibular labyrinth, hair cells are capable of generating axial deformations in response to variations in transmembrane potential. Our understanding of electromechanical transduction in the hair cells depends on precise knowledge of intracellular structure, and efforts to model hair cell physiology are likewise limited to the fidelity of known intracellular geometry. This collaboration focuses on the ultrastructure of vestibular hair cells. More precisely, we are looking at the subcuticular region (below the cuticular plate), using electron tomography to visualize and analyze rootlet architecture at the junction of the stereocilia bundle and apical region of the cell. Our main interest is the striated organelle (SO), a unique structure located at the apical end of hair cells (auditory and vestibular sensory cells), just below the cuticular plate. It is particularly prominent in mammalian type I vestibular hair cells. The central hypothesis we are investigating with aid from the NCMIR is that striated organelles provide structural and functional connections between the apical and basal parts of the hair cell. The goals of this joint effort are to describe the three-dimensional structure of this particular organelle and to identify its components (or at least, some of the components). Our study should appeal to: 1) sensory physiologists interested in mechanisms of sensory transduction and mechanotransduction, 2) neuroscientists interested in feedback from afferents to the transduction apparatus, 3) protein chemists interested in potential new motor proteins, contractile elements, calcium dynamics, and the molecular architecture of these mechanisms, 4) molecular and cell biologists interested in actin, molecular motors, the cytoskeleton and mitochondria, and 5) microscopists and morphologists interested in a new and elegant structural apparatus.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR004050-23
Application #
8361921
Study Section
Special Emphasis Panel (ZRG1-BST-R (40))
Project Start
2011-04-01
Project End
2012-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
23
Fiscal Year
2011
Total Cost
$24,666
Indirect Cost
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Funakoshi, Shunsuke; Miki, Kenji; Takaki, Tadashi et al. (2016) Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes. Sci Rep 6:19111
Rubio-Marrero, Eva N; Vincelli, Gabriele; Jeffries, Cy M et al. (2016) Structural Characterization of the Extracellular Domain of CASPR2 and Insights into Its Association with the Novel Ligand Contactin1. J Biol Chem 291:5788-802
Yin, Xinghua; Kidd, Grahame J; Ohno, Nobuhiko et al. (2016) Proteolipid protein-deficient myelin promotes axonal mitochondrial dysfunction via altered metabolic coupling. J Cell Biol 215:531-542
Zhao, Claire Y; Greenstein, Joseph L; Winslow, Raimond L (2016) Roles of phosphodiesterases in the regulation of the cardiac cyclic nucleotide cross-talk signaling network. J Mol Cell Cardiol 91:215-27
Rajagopal, Vijay; Bass, Gregory; Walker, Cameron G et al. (2015) Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes. PLoS Comput Biol 11:e1004417
Schachtrup, Christian; Ryu, Jae Kyu; Mammadzada, Könül et al. (2015) Nuclear pore complex remodeling by p75(NTR) cleavage controls TGF-? signaling and astrocyte functions. Nat Neurosci 18:1077-80
Sanders, Matthew A; Madoux, Franck; Mladenovic, Ljiljana et al. (2015) Endogenous and Synthetic ABHD5 Ligands Regulate ABHD5-Perilipin Interactions and Lipolysis in Fat and Muscle. Cell Metab 22:851-60
Takeshima, Hiroshi; Hoshijima, Masahiko; Song, Long-Sheng (2015) Ca²? microdomains organized by junctophilins. Cell Calcium 58:349-56
Mills, Elizabeth A; Davis, Chung-ha O; Bushong, Eric A et al. (2015) Astrocytes phagocytose focal dystrophies from shortening myelin segments in the optic nerve of Xenopus laevis at metamorphosis. Proc Natl Acad Sci U S A 112:10509-14
Kim, K-Y; Perkins, G A; Shim, M S et al. (2015) DRP1 inhibition rescues retinal ganglion cells and their axons by preserving mitochondrial integrity in a mouse model of glaucoma. Cell Death Dis 6:e1839

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