Thursday, January 1, 2026 1/1/2026

Actin regulation by cyclase-associated protein

Award Number: R01GM144563
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/11/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2027

Group Awards By:

View Award Description

Actin regulation by cyclase-associated protein - Project Summary Reorganization of the actin cytoskeleton supports many dynamic cell biological processes, such as cell migration, cytokinesis, vesicle trafficking, and morphogenesis. Although actin spontaneously polymerizes and depolymerizes by itself, the dynamic properties of actin need to be controlled by actin-regulatory proteins in cells. Among many known actin-regulatory proteins, cyclase-associated protein (CAP) regulates multiple key processes of actin dynamics. CAP is conserved among eukaryotes and has been known as an actin-monomer binding protein for many years. However, recent studies have identified important functions of CAP, which are critical to promote rapid actin turnover. CAP promotes disassembly of actin filaments from the pointed ends in the presence of actin-depolymerizing factor (ADF)/cofilin. Spontaneous actin depolymerization from the pointed ends is very slow and rate-limiting in actin filament turnover. The synergy between CAP and ADF/cofilin can enhance actin depolymerization in vitro to a range that can explain rapid actin turnover in cells. However, the precise mechanism by which CAP and ADF/cofilin induce actin depolymerization remains unclear, partly because structural information of a CAP oligomer is limited. CAP oligomerizes under physiological conditions, and oligomerization enhances its activity. We have recently obtained evidence that CAP is tetrameric, and our structural model of the CAP tetramer allowed us to hypothesize a functional link between the tetrameric configuration of CAP and processive actin depolymerizing activity. CAP also binds to the side of actin filaments and synergizes with ADF/cofilin to promote filament severing. We hypothesize that this is due to the effect of CAP on the helical structures of actin filaments, which then causes partial dissociation of ADF/cofilin from the filaments. In addition to the in vitro studies, recent reports of human mutations in the CAP (CAP2) gene have linked impairment of CAP to human diseases in the heart and skeletal muscle involving abnormalities in the actin cytoskeletal organization. We will use the nematode Caenorhabditis elegans as a relevant model organism to study roles of CAP in the assembly of sarcomeric actin filaments in muscle cells in vivo. We proposes three aims: (1) to determine functional significance of CAP tetramerization for actin filament disassembly, (2) to determine the effects of CAP on the helical structures of F-actin, and (3) to determine in vivo roles of CAP in actin cytoskeletal integrity in the nematode Caenorhabditis elegans. We will employ a combination of in vitro and in vivo approaches to gain new insight in the function of CAP in actin cytoskeletal regulation.


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: 2026 ( Subtotal = $281,700 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Biomedical Research and Research Training	000	3	12/9/2025	NON-COMPETING CONTINUATION	$281,700
														Subtotal = $281,700

Issue Date FY: 2025 ( Subtotal = $313,000 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Biomedical Research and Research Training	000	2	11/21/2024	NON-COMPETING CONTINUATION	$281,700
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Biomedical Research and Research Training	001	2	8/12/2025	NON-COMPETING CONTINUATION	$31,300
														Subtotal = $313,000

Issue Date FY: 2024 ( Subtotal = $313,000 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Biomedical Research and Research Training	000	1	12/11/2023	NEW	$313,000
														Subtotal = $313,000

Grand Total All Awards = $907,700

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Actin regulation by cyclase-associated protein

Award Number: R01GM144563

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/11/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer