Calcium-regulated release of neurotransmitter is a fundamental feature of synaptic communication. How this process is regulated presynaptically is not yet fully understood, particularly at the ribbon-style synapses of retinal photoreceptors and bipolar cells. These synapses differ from conventional synapses in several important ways, including the expression of unusual isoforms of key synaptic proteins and the absence of other synaptic proteins. Thus, it is not clear to what extent knowledge of presynaptic mechanisms obtained in other model systems can be extrapolated to these neurons. Furthermore, mutations in some of these unusual proteins are associated with human retinal disease. The long-term goal of this research project is to understand how visual information is transferred across the retina. In this proposal, we examine mechanisms of exocytosis and synaptic vesicle dynamics in bipolar cells and photoreceptors of the vertebrate retina. This information will reveal aspects of presynaptic design that allows these neurons to release glutamate rapidly and for extended periods of time. A combination of biophysical, ultrastructural, and molecular approaches are used. Specific goals are to examine the mechanisms underlying the requirement for ATP hydrolysis in maintaining neurotransmitter release and endocytosis in ON-bipolar cells. Because endocytosis may contribute to the supply of active zone synaptic vesicles in addition to preserving membrane surface area, mechanisms of membrane retrieval in bipolar cells and photoreceptors will also be examined. To allow us to determine in what ways photoreceptors are adapted for tonic release and to define those presynaptic mechanisms that are hallmarks of retinal ribbon synapses, synaptic vesicle dynamics in photoreceptors will be examined and compared with those of bipolar cells and conventional synapses. Finally, we will develop the mouse bipolar cell as a preparation for biophysical study of presynaptic mechanisms. This will position us to study presynaptic mechanisms at the molecular level and examine the role of specific synaptic proteins implicated in disorders of vision. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012128-10
Application #
7230923
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Mariani, Andrew P
Project Start
1998-05-01
Project End
2008-08-31
Budget Start
2007-05-01
Budget End
2008-08-31
Support Year
10
Fiscal Year
2007
Total Cost
$324,447
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Neurosciences
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Gutierrez, Berenice A; Chavez, Miguel A; Rodarte, Alejandro I et al. (2018) Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle-regulated exocytosis in mast cells. J Biol Chem 293:7148-7159
Datta, Proleta; Gilliam, Jared; Thoreson, Wallace B et al. (2017) Two Pools of Vesicles Associated with Synaptic Ribbons Are Molecularly Prepared for Release. Biophys J 113:2281-2298
Liu, Xiaoqin; Heidelberger, Ruth; Janz, Roger (2014) Phosphorylation of syntaxin 3B by CaMKII regulates the formation of t-SNARE complexes. Mol Cell Neurosci 60:53-62
Chen, Shuyi; Li, Hua; Gaudenz, Karin et al. (2013) Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis. Cell Res 23:254-73
Wan, Qun-Fang; Nixon, Everett; Heidelberger, Ruth (2012) Regulation of presynaptic calcium in a mammalian synaptic terminal. J Neurophysiol 108:3059-67
Frazao, Renata; McMahon, Douglas G; Schunack, Walter et al. (2011) Histamine elevates free intracellular calcium in mouse retinal dopaminergic cells via H1-receptors. Invest Ophthalmol Vis Sci 52:3083-8
Wan, Qun-Fang; Heidelberger, Ruth (2011) Synaptic release at mammalian bipolar cell terminals. Vis Neurosci 28:109-19
Duncan, Gabriel; Rabl, Katalin; Gemp, Ian et al. (2010) Quantitative analysis of synaptic release at the photoreceptor synapse. Biophys J 98:2102-10
Curtis, L; Datta, P; Liu, X et al. (2010) Syntaxin 3B is essential for the exocytosis of synaptic vesicles in ribbon synapses of the retina. Neuroscience 166:832-41
Wan, Qun-Fang; Zhou, Zhen-Yu; Thakur, Pratima et al. (2010) SV2 acts via presynaptic calcium to regulate neurotransmitter release. Neuron 66:884-95

Showing the most recent 10 out of 14 publications