The NHL-domain protein Wech is crucial for the integrin-cytoskeleton link.
Integrin transmembrane receptors mediate cell adhesion through intracellular linker proteins that connect to the cytoskeleton. Of the numerous linker proteins identified, only a few, including Talin and Integrin-linked-kinase (ILK), are essential and evolutionarily conserved. The wech gene encodes a newly discovered and highly conserved regulator of integrin-mediated adhesion in Drosophila melanogaster. Embryos deficient in wech have very similar phenotypes to integrin-null or Talin-null embryos, including muscle detachment from the body wall. The Wech protein contains a B-box zinc-finger and a coiled-coil domain, which is also found in RBCC/TRIM family members, and an NHL domain. In beta-integrin or Talin mutants, Wech is mislocalized, whereas ILK localization depends on Wech. We provide evidence that Wech interacts with the head domain of Talin and the kinase domain of ILK, and propose that Wech is required to connect both core proteins of the linker complex during embryonic muscle attachment. Both the NHL and the B-box/coiled-coil domains of Wech are required for proper interaction with Talin and ILK. The single murine Wech orthologue is also colocalized with Talin and ILK in muscle tissue. We propose that Wech proteins are crucial and evolutionarily conserved regulators of the integrin-cytoskeleton link.
Löer
Birgit
B
Life and Medical Sciences Institute (LIMES), Program Unit Development & Genetics, Laboratory for Molecular Developmental Biology, University of Bonn, Meckenheimer Allee 169, D-53115 Bonn, Germany.
Bauer
Reinhard
R
Bornheim
Roland
R
Grell
Jessica
J
Kremmer
Elisabeth
E
Kolanus
Waldemar
W
Hoch
Michael
M
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016608:Talin / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D029721:Drosophila Proteins; D016023:Integrins; D011993:Recombinant Fusion Proteins; D016608:Talin; C528683:Wech protein, Drosophila