Research ArticleCell Biology

Hereditary spastic paraplegia SPG8 mutations impair CAV1-dependent, integrin-mediated cell adhesion

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Science Signaling  07 Jan 2020:
Vol. 13, Issue 613, eaau7500
DOI: 10.1126/scisignal.aau7500

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Disease-associated mutations impair integrin recycling

Hereditary spastic paraplegia (HSP) type SPG8 is an inherited neurologic disorder associated with mutations in WASHC5, which encodes strumpellin, a component of the WASH complex, which localizes to endosomes and plays a role in endosomal sorting. Lee et al. found that strumpellin interacted with the caveolar protein CAV1 and inhibited its degradation. Cultured cells lacking strumpellin or expressing SPG8-associated strumpellin mutants exhibited impaired endosomal tubulation, reduced CAV1 at intracellular vesicles, and reduced integrin-mediated cell adhesion. The actin nucleation activity of the WASH complex was required for inhibiting the degradation of CAV1 and integrin α5, and the interaction between strumpellin and CAV1 was required for proper recycling of integrin α5 and for integrin-mediated cell adhesion. These findings suggest that the axon defects that characterize HSP type SPG8 may be due to disruption of strumpellin- and CAV1-dependent, integrin-mediated cell adhesion.

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