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bioRxiv · 10.64898/2026.10.28.762573

STRIPAK associates with Rabex5-Rabaptin5 to promote Rab5-dependent early endosome formation and EGFR transport

Woodman, P.·Francavilla, C.·Sugar, S. N.·Wunderley, L.·Trotter, E. W.·Shimizu, H.·Parkinson, G.·Fullwood, P.
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Abstract

His Domain Protein Tyrosine Phosphatase (HD-PTP) is required for multivesicular body (MVB) formation and endosome maturation, with Rab5-GTP levels raised upon HD-PTP depletion (Parkinson et al., 2021. doi: 10/1242/jcs.259192). Mass Spectrometry-based interactomics revealed that HD-PTP depletion increased association of Rabaptin5, a component of the early endosome Rabex5-Rabaptin5 Rab5-GEF, with multiple components of STRIPAK (striatin-interacting phosphatase and kinase). Native IPs and co-expression studies confirmed association between STRIPAK and Rabex5-Rabaptin5, including Strip1-Rabex5 and SLMAP-Rabaptin5 interactions. Consistent with functional Rabaptin5-STRIPAK links, co-depletion of Strip1 or Rabaptin5 with HD-PTP restored normal early endosome positioning and Rab5 distribution. Strip1 depletion impaired formation of central, Rab5-positive early endosomes, reduced cellular Rab5-GTP levels, and prevented the accumulation of internalised EGF-EGFR into centrally located endosomes. SLMAP depletion accentuated the central clustering of early endosomes and other endosomal compartments while also retarding the generation of new, EGFR-containing endosomes and EGFR lysosomal transport. We conclude that STRIPAK is a novel co-assembly factor of Rabex5-Rabaptin5, exerting subunit-specific effects on early endosomes.

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Woodman, P., Francavilla, C., Sugar, S. N., Wunderley, L., Trotter, E. W., Shimizu, H., Parkinson, G., Fullwood, P.. 2026-10-30. STRIPAK associates with Rabex5-Rabaptin5 to promote Rab5-dependent early endosome formation and EGFR transport. https://doi.org/10.64898/2026.10.28.762573

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