RRC ID 53962
著者 Gotenstein JR, Koo CC, Ho TW, Chisholm AD.
タイトル Genetic Suppression of Basement Membrane Defects in Caenorhabditis elegans by Gain of Function in Extracellular Matrix and Cell-Matrix Attachment Genes.
ジャーナル Genetics
Abstract Basement membranes are extracellular matrices essential for embryonic development in animals. Peroxidasins are extracellular peroxidases implicated in the unique sulfilimine cross-links between type IV basement membrane collagens. Loss of function in the Caenorhabditis elegans peroxidasin PXN-2 results in fully penetrant embryonic or larval lethality. Using genetic suppressor screening, we find that the requirement for PXN-2 in development can be bypassed by gain of function in multiple genes encoding other basement membrane components, or proteins implicated in cell-matrix attachment. We identify multiple alleles of let-805, encoding the transmembrane protein myotactin, which suppress phenotypes of pxn-2 null mutants and of other basement membrane mutants such as F-spondin/spon-1 These let-805 suppressor alleles cause missense alterations in two pairs of FNIII repeats in the extracellular domain; they act dominantly and have no detectable phenotypes alone, suggesting they cause gain of function. We also identify suppressor missense mutations affecting basement membrane components type IV collagen (emb-9, let-2) and perlecan (unc-52), as well as a mutation affecting spectraplakin (vab-10), a component of the epidermal cytoskeleton. These suppressor alleles do not bypass the developmental requirement for core structural proteins of the basement membrane such as laminin or type IV collagen. In conclusion, putative gain-of-function alterations in matrix proteins or in cell-matrix receptors can overcome the requirement for certain basement membrane proteins in embryonic development, revealing previously unknown plasticity in the genetic requirements for the extracellular matrix.
巻・号 208(4)
ページ 1499-1512
公開日 2018-4-1
DOI 10.1534/genetics.118.300731
PII genetics.118.300731
PMID 29440357
PMC PMC5887144
MeSH Animals Basement Membrane / metabolism* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Chromosome Mapping Clustered Regularly Interspaced Short Palindromic Repeats Collagen Type IV / genetics Collagen Type IV / metabolism Cytoskeleton Extracellular Matrix / metabolism* Extracellular Matrix Proteins / genetics* Extracellular Matrix Proteins / metabolism* Gain of Function Mutation Gene Expression Gene Knock-In Techniques Genes, Reporter Loss of Function Mutation Mutation Peroxidase / genetics Peroxidase / metabolism Peroxiredoxins / genetics Peroxiredoxins / metabolism Phenotype Protein Transport Whole Genome Sequencing
IF 4.015
引用数 3
リソース情報
線虫 tm3464