De novo talin-1 variant L353F connects multifaceted clinical symptoms to alterations in talin-1 function.

ABSTRACT: Talin-1 is a central integrin adapter protein connecting cytoplasmic domains of integrins to the cytoskeleton. These talin-1-mediated mechanical linkages are crucial for cellular functions such as cell movement and connections with other cells. Here, we report a patient carrying a missense variant, L353F, in the talin-1 head which is associated with a complex set of symptoms, including skin lesions, blood cell abnormalities, and congenital cataracts. We conducted structural and cellular characterization of this variant. Recombinant talin-1 F2F3 fragment with the corresponding mutation showed a decrease in thermal stability and decreased solubility. Reconstitution of talin-deficient cells with L353F talin-1 revealed decreased cell migration velocity, defects in wound healing capacity, and c

SUBMITTER: Athale M 

PROVIDER: S-EPMC12599238 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature