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GJA1-20K is a new regulator of actin dynamics and myocardial cell-cell coupling

Award Number: F31HL147404
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 09/07/2021

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GJA1-20K is a new regulator of actin dynamics and myocardial cell-cell coupling - PROJECT SUMMARY – ABSTRACT Heart disease is the leading cause of the death in the United States. In the heart, Connexin 43 (Cx43) gap junctions are integral to healthy heart function and synchronized muscle contraction by allowing ion passage between cardiomyocytes. Cx43 is encoded by the GJA1 gene in a single coding exon, but GJA1 mRNA contains six internal methionine start sites, which encode six small isoforms of Cx43 that retain the same C-terminus tail. GJA1-20k, the 20 kDa isoform, is the most abundantly expressed, and the Shaw laboratory has discovered that it is necessary for trafficking Cx43 along microtubules from the nucleus to the cell membrane. Recent work from our group shows that the actin cytoskeleton is also required for Cx43 trafficking, both as cargo rest stops and for proper microtubule orientation to the cell membrane. We have also shown that GJA1-20k expression in both HeLa cells and cardiomyocytes results in an increase in total and thicker actin fibers in the cell and stabilizes actin filaments against Latrunculin A treatment, but a direct interaction between GJA1-20k and actin has never been studied. In Aim 1, I will utilize cell free TIRF imaging of actin dynamics to uncover the role of GJA1-20k as an actin binding protein. I will use mutagenesis to find the binding site between GJA1-20k and actin. In Aim 2, I will use isolated cardiomyocytes to see how GJA1-20k mediated actin stabilization protects the formation and function of gap junction plaques. These results will uncover GJA1-20k as a novel actin binding protein and provide better understanding of how GJA1-20k utilizes its interaction with actin to protect gap junction plaque formation in the heart.


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: 2023 ( Subtotal = -$32,350 )
2023	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	001	3	11/23/2022	NON-COMPETING CONTINUATION	-$12,667
2023	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	2	11/23/2022	NON-COMPETING CONTINUATION	-$19,683
														Subtotal = -$32,350

Issue Date FY: 2022 ( Subtotal = -$33,369 )
2022	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	3	8/30/2022	NON-COMPETING CONTINUATION	-$33,369
														Subtotal = -$33,369

Issue Date FY: 2021 ( Subtotal = $46,036 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	3	3/16/2021	NON-COMPETING CONTINUATION	$46,036
														Subtotal = $46,036

Issue Date FY: 2020 ( Subtotal = $45,520 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	2	4/1/2020	NON-COMPETING CONTINUATION	$45,520
														Subtotal = $45,520

Issue Date FY: 2019 ( Subtotal = $45,016 )
2019	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	001	1	3/21/2019	NEW	$0
2019	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cardiovascular Diseases Research	000	1	3/21/2019	NEW	$45,016
														Subtotal = $45,016

Grand Total All Awards = $70,853

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GJA1-20K is a new regulator of actin dynamics and myocardial cell-cell coupling

Award Number: F31HL147404

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 09/07/2021

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