STRIPAK associates with Rabex5-Rabaptin5 to promote Rab5-dependent early endosome formation and EGFR transport
- 1University of Manchester
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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BibTeX
@misc{woodman2026stripak,
title = {{STRIPAK associates with Rabex5-Rabaptin5 to promote Rab5-dependent early endosome formation and EGFR transport}},
author = {P. Woodman and C. Francavilla and S. N. Sugar and L. Wunderley and E. W. Trotter and H. Shimizu and G. Parkinson and P. Fullwood},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762573},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762573v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - STRIPAK associates with Rabex5-Rabaptin5 to promote Rab5-dependent early endosome formation and EGFR transport
AU - P. Woodman
AU - C. Francavilla
AU - S. N. Sugar
AU - L. Wunderley
AU - E. W. Trotter
AU - H. Shimizu
AU - G. Parkinson
AU - P. Fullwood
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762573
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762573v1
AB - 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.
ER -