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Regulation of Retinal Gap Junctions

Award Number: R01EY012857
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/18/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Regulation of Retinal Gap Junctions - Synaptic communication in the nervous system is accomplished by two major classes of synapses, chemical and electrical, which operate in different ways. Electrical synapses are formed by gap junctions between neurons and allow passage of electrical current directly between cells, providing fast and often bi-directional communication. Cellular control of the magnitude of this communication refines local and long-range neural network functions, and is an important component of network plasticity. Electrical synapse plasticity plays a particularly important role in sensory adaptation in the vertebrate retina, where changes in coupling of some networks exceed an order of magnitude. The long-term goals of this established research project are to elucidate the mechanisms that control plasticity of electrical synapses. In recent work, we have discovered an intimate relationship between the actin cytoskeleton and functional control of coupling in Connexin 36 (Cx36) gap junctions. This appears to integrate the main components of excitatory and inhibitory signaling and switching between those modes. This project will investigate those links, using a combination of cell culture and mouse retina model systems. We will test three specific hypotheses about regulation of Cx36 functional coupling in the following ways: (1) Signaling protein complexes that regulate Cx36 coupling are associated with the actin cytoskeleton. Using proximity labeling and quantitative proteomic techniques, we will identify signaling components involved in the regulation of Cx36 coupling. We will further investigate the dynamic changes in proximity of these components to Cx36 during regulatory signaling. (2) Phosphorylation of Cx36 alters its association with signaling components. We will investigate how phosphorylation of certain residues of Cx36 regulates the association of some signaling components. (3) RhoA and Cdc42 signaling pathways modulate functional plasticity. We will investigate how pathways that control cytoskeletal remodeling influence coupling of Cx36. The proposed studies will elucidate mechanisms central to control of electrical synapse functional plasticity. Knowledge of these mechanisms will provide a great deal of insight not only into the control of visual adaptation processes in the retina, but also electrical synapse plasticity throughout the brain. This will allow the development of targeted therapies for disorders in which gap junctions play a role.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $667,528 )
2025	2025	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Vision Research	001	21	6/27/2025	COMPETING CONTINUATION	$667,528
2025	2024	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Vision Research	000	20	6/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $667,528

Issue Date FY: 2024 ( Subtotal = $404,459 )
2024	2024	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Vision Research	000	20	3/1/2024	NON-COMPETING CONTINUATION	$404,459
														Subtotal = $404,459

Issue Date FY: 2023 ( Subtotal = $404,459 )
2023	2023	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Vision Research	000	19	2/27/2023	NON-COMPETING CONTINUATION	$404,459
														Subtotal = $404,459

Issue Date FY: 2022 ( Subtotal = $412,569 )
2022	2022	UNIVERSITY OF HOUSTON SYSTEM	4800 W CALHOUN ST STE 316	HOUSTON	TX	77004	HARRIS	USA	Vision Research	004	18	6/6/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$272,118
2022	2022	UNIVERSITY OF HOUSTON SYSTEM	4800 W CALHOUN ST STE 316	HOUSTON	TX	77004	HARRIS	USA	Vision Research	001	18	4/7/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$411,725
2022	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	17	4/7/2022	COMPETING CONTINUATION	$0
2022	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Vision Research	002	17	5/26/2022	COMPETING CONTINUATION	$844
2022	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Vision Research	003	17	6/6/2022	COMPETING CONTINUATION	-$272,118
														Subtotal = $412,569

Issue Date FY: 2021 ( Subtotal = $441,224 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Vision Research	001	17	2/22/2021	COMPETING CONTINUATION	$442,068
2021	2018	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	16	1/11/2021	NON-COMPETING CONTINUATION	-$844
														Subtotal = $441,224

Issue Date FY: 2018 ( Subtotal = $402,066 )
2018	2018	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	16	4/24/2018	NON-COMPETING CONTINUATION	$402,066
														Subtotal = $402,066

Issue Date FY: 2017 ( Subtotal = $402,066 )
2017	2017	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST STE 1006	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	15	4/20/2017	NON-COMPETING CONTINUATION	$361,858
2017	2017	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST STE 1006	HOUSTON	TX	77030	HARRIS	USA	Vision Research	001	15	7/7/2017	NON-COMPETING CONTINUATION	$40,208
														Subtotal = $402,066

Issue Date FY: 2016 ( Subtotal = $424,066 )
2016	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	14	4/22/2016	NON-COMPETING CONTINUATION	$424,066
														Subtotal = $424,066

Issue Date FY: 2015 ( Subtotal = $422,066 )
2015	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	13	4/7/2015	COMPETING CONTINUATION	$422,066
														Subtotal = $422,066

Issue Date FY: 2014 ( Subtotal = $52,715 )
2014	2014	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	POST OFFICE BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	001	12	4/21/2014	SUPPLEMENT FOR EXPANSION	$0
2014	2014	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	12	2/26/2014	SUPPLEMENT FOR EXPANSION	$52,715
2014	2013	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	POST OFFICE BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	002	12	4/21/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $52,715

Issue Date FY: 2013 ( Subtotal = $342,000 )
2013	2013	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	POST OFFICE BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	002	12	4/21/2014	NON-COMPETING CONTINUATION	$0
2013	2013	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	001	12	6/13/2013	NON-COMPETING CONTINUATION	$18,000
2013	2013	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	12	4/24/2013	NON-COMPETING CONTINUATION	$324,000
														Subtotal = $342,000

Issue Date FY: 2012 ( Subtotal = $459,127 )
2012	2012	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	001	11	9/11/2012	SUPPLEMENT FOR EXPANSION	$99,127
2012	2012	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	11	3/14/2012	NON-COMPETING CONTINUATION	$360,000
														Subtotal = $459,127

Issue Date FY: 2011 ( Subtotal = $360,000 )
2011	2011	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	10	3/17/2011	NON-COMPETING CONTINUATION	$337,500
2011	2011	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	001	10	6/16/2011	NON-COMPETING CONTINUATION	$22,500
														Subtotal = $360,000

Issue Date FY: 2010 ( Subtotal = $375,000 )
2010	2010	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	P.O. BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	9	3/16/2010	COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 2008 ( Subtotal = $316,659 )
2008	2008	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	POST OFFICE BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	8	3/3/2008	NON-COMPETING CONTINUATION	$316,659
														Subtotal = $316,659

Issue Date FY: 2007 ( Subtotal = $323,159 )
2007	2007	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	POST OFFICE BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	7	1/31/2007	NON-COMPETING CONTINUATION	$323,159
														Subtotal = $323,159

Issue Date FY: 2006 ( Subtotal = $357,849 )
2006	2006	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	POST OFFICE BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	6	2/24/2006	COMPETING CONTINUATION	$357,849
														Subtotal = $357,849

Issue Date FY: 2004 ( Subtotal = $184,578 )
2004	2004	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	POST OFFICE BOX 20036	HOUSTON	TX	77225	HARRIS	USA	Vision Research	000	5	2/6/2004	NON-COMPETING CONTINUATION	$184,578
														Subtotal = $184,578

Issue Date FY: 2003 ( Subtotal = $179,259 ) (Continued on the next page)
Grand Total All Awards = $7,596,261

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Regulation of Retinal Gap Junctions

Award Number: R01EY012857

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/18/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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