Rab10-CAV1 mediated intraluminal vesicle transport to migrasomes

Proc Natl Acad Sci U S A. 2024 Jul 23;121(30):e2319267121. doi: 10.1073/pnas.2319267121. Epub 2024 Jul 15.

Abstract

Migrasomes, vesicular organelles generated on the retraction fibers of migrating cells, play a crucial role in migracytosis, mediating intercellular communication. The cargoes determine the functional specificity of migrasomes. Migrasomes harbor numerous intraluminal vesicles, a pivotal component of their cargoes. The mechanism underlying the transportation of these intraluminal vesicles to the migrasomes remains enigmatic. In this study, we identified that Rab10 and Caveolin-1 (CAV1) mark the intraluminal vesicles in migrasomes. Transport of Rab10-CAV1 vesicles to migrasomes required the motor protein Myosin Va and adaptor proteins RILPL2. Notably, the phosphorylation of Rab10 by the kinase LRRK2 regulated this process. Moreover, CSF-1 can be transported to migrasomes through this mechanism, subsequently fostering monocyte-macrophage differentiation in skin wound healing, which served as a proof of the physiological importance of this transporting mechanism.

Keywords: Caveolin 1; Rab GTPases; migrasome; vesicle trafficking.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Biological Transport
  • Caveolin 1* / genetics
  • Caveolin 1* / metabolism
  • Cell Movement*
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
  • Macrophages / metabolism
  • Mice
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Myosin Type V / genetics
  • Myosin Type V / metabolism
  • Organelles / metabolism
  • Phosphorylation
  • Wound Healing / physiology
  • rab GTP-Binding Proteins* / genetics
  • rab GTP-Binding Proteins* / metabolism

Substances

  • rab GTP-Binding Proteins
  • Caveolin 1
  • Rab10 protein, human
  • Adaptor Proteins, Signal Transducing
  • Myosin Type V
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Myosin Heavy Chains