Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The tetraspanin CD151 and integrin α3β1 signaling complex in basement membrane adhesion

Award Number: F31AR083740
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2027

Group Awards By:

View Award Description

The tetraspanin CD151 and integrin α3β1 signaling complex in basement membrane adhesion - Project Summary The structural integrity of the skin is dependent on appropriate cell attachment to the basement membrane, which forms the foundation of the epidermis and separates it from the dermis. Laminins are the major component of the basement membrane, where integrin receptors form adhesive contacts and connect the intracellular cytoskeleton to the extracellular matrix. Integrins are heterodimeric adhesion receptors that link cells to components of the extracellular matrix and to other cells, and they are essential for cell adhesion, migration, and multicellularity. Laminin binding integrins are fundamental in attaching epithelial cells to the basement membrane. In humans, a well conserved family of proteins, the tetraspanins, have been shown to bind and form signaling complexes with laminin-binding integrins. Tetraspanins are a class of four-pass transmembrane domain proteins with diverse biological roles involving modulation of the trafficking, membrane localization, and signaling of their various partners. The interaction between tetraspanins and integrins remains an exciting area of research as in vivo evidence suggests the interaction is necessary for normal integrin function. The tetraspanin CD151 binds all laminin binding integrins but associates most stably with the laminin-binding integrin α3β1 (ITGα3β1). Silencing mutations in either CD151 and ITGα3β1 both result in epidermolysis bullosa (EB), a disease phenotype consistent with impaired laminin binding and basement membrane attachment. However, why integrin function is diminished in this disease remains unclear, and whether CD151 affects ITGα3β1conformation or affects its activity through other signaling mechanisms is unresolved. Integrins characteristically exist in three conformations which each conferring different ligand affinity. CD151 may bind to and stabilize a specific ITGα3β1 conformation. This proposal will use structural approaches to determine if ITGα3β1 signaling is CD151 dependent due to conformation regulation. Additionally, signaling may be dependent on other downstream signaling mechanisms. I will use a proximity labeling time course approach to define the dynamic response to integrin activation and the influence of CD151 on ITGα3β1 signaling. These approaches will determine how CD151 modulates ITGα3β1, which can be applied to understand general tetraspanin and laminin binding integrin signaling biology. Although tetraspanins have many interaction partners and are implicated in various biological processes, the mechanism by which they engage and modulate their binding partners remains understudied. Specifically, understanding the CD151-ITGα3β1 signaling complex and its role in epidermal adhesion could be exploited therapeutically to strengthen epidermis attachment in EB and potentially other diseases of the skin.


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 = $36,822 )
2026	2026	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	3	3/31/2026	NON-COMPETING CONTINUATION	$576
2026	2026	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	2/5/2026	NON-COMPETING CONTINUATION	$35,682
2026	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	2/26/2026	NON-COMPETING CONTINUATION	$564
														Subtotal = $36,822

Issue Date FY: 2025 ( Subtotal = $35,118 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/7/2025	NON-COMPETING CONTINUATION	$35,118
														Subtotal = $35,118

Issue Date FY: 2024 ( Subtotal = $41,403 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	5/17/2024	NEW	$1,280
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/1/2024	NEW	$40,123
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	3/1/2024	NEW	$0
														Subtotal = $41,403

Grand Total All Awards = $113,343

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The tetraspanin CD151 and integrin α3β1 signaling complex in basement membrane adhesion

Award Number: F31AR083740

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer