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The kinesin KIF3AC recycles endocytosed integrin to polarize adhesion formation towards the leading edge. | LitMetric

AI Article Synopsis

  • * The kinesin-2 heterodimer, KIF3AC, along with the Rab11 adaptor protein RCP, are necessary for the reformation of focal adhesions in both mouse and human fibroblasts.
  • * KIF3AC facilitates the trafficking of integrin to the cell surface after it is internalized, promoting polarized cell migration and new focal adhesion formation.

Article Abstract

Unlabelled: The recycling of integrin endocytosed during focal adhesion (FA) disassembly is critical for cell migration and contributes to the polarized formation of new FAs toward the leading edge. How this occurs is unclear. Here, we sought to identify the kinesin motor protein(s) that is involved in recycling endocytosed integrin back to the plasma membrane. We show that the kinesin-2 heterodimer, KIF3AC and the Rab11 adaptor protein RCP are required for FA reformation after the disassembly of FAs in mouse and human fibroblasts. In the absence of KIF3AC, integrin does not return to the cell surface after FA disassembly and is found in the Rab11 endocytic recycling compartment. Biochemical pulldowns revealed that KIF3C associated with β1 integrin in an RCP dependent fashion, but only after FA disassembly. KIF3AC knockdown inhibited cell migration, trafficking of RCP toward the leading edge, and polarized formation of FAs at the leading edge. These results show that KIF3AC promotes cell migration by recycling integrin so that it generates new FAs in a polarized fashion.

Summary: The study reveals that the heterodimeric kinesin-2 motor KIF3AC and its adaptor RCP are crucial for polarized formation of focal adhesions at the front of migrating fibroblasts. KIF3AC and RCP associate with intracellularly recycling integrin to promote its return to the cell surface after its endocytosis from disassembled focal adhesions.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661233PMC
http://dx.doi.org/10.1101/2024.12.09.627580DOI Listing

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