α-Integrins dictate distinct modes of type IV collagen recruitment to basement membranes

The Journal of Cell Biology
Ranjay JayadevDavid R Sherwood

Abstract

Basement membranes (BMs) are cell-associated extracellular matrices that support tissue integrity, signaling, and barrier properties. Type IV collagen is critical for BM function, yet how it is directed into BMs in vivo is unclear. Through live-cell imaging of endogenous localization, conditional knockdown, and misexpression experiments, we uncovered distinct mechanisms of integrin-mediated collagen recruitment to Caenorhabditis elegans postembryonic gonadal and pharyngeal BMs. The putative laminin-binding αINA-1/βPAT-3 integrin was selectively activated in the gonad and recruited laminin, which directed moderate collagen incorporation. In contrast, the putative Arg-Gly-Asp (RGD)-binding αPAT-2/βPAT-3 integrin was activated in the pharynx and recruited high levels of collagen in an apparently laminin-independent manner. Through an RNAi screen, we further identified the small GTPase RAP-3 (Rap1) as a pharyngeal-specific PAT-2/PAT-3 activator that modulates collagen levels. Together, these studies demonstrate that tissues can use distinct mechanisms to direct collagen incorporation into BMs to precisely control collagen levels and construct diverse BMs.

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Citations

Aug 30, 2019·Journal of Developmental Biology·Devyn OliverMichele L Lemons
Apr 23, 2020·Journal of Cell Science·José C Pastor-Pareja
Aug 26, 2020·Nature Reviews. Nephrology·Richard W NaylorRachel Lennon
Jan 21, 2021·Bioengineering·Yujia Xu, Michele Kirchner
Sep 21, 2020·Progress in Retinal and Eye Research·Sayon Roy, Dongjoon Kim
Apr 16, 2021·Cellular Signalling·Aqilah AmranSandeep Gopal
Jan 1, 2020·Journal of Microbiology & Biology Education·Eric HastieDavid R Sherwood
May 21, 2021·Current Opinion in Cell Biology·David R Sherwood
Jul 16, 2021·Ecotoxicology and Environmental Safety·Ying ZhangLihong Yin

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Methods Mentioned

BETA
GTPase
Fluorescence
transgenic
RAP-3
nucleotide exchange
PCR

Software Mentioned

Imaris
flexlink
ImageJ
Fiji
μManager

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