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

STRIPAK subunits associate with Rabex5-Rabaptin5 to regulate Rab5-dependent early endosome formation and EGFR transport, with Strip1 depletion lowering Rab5-GTP and central endosomes.

• Why it matters: HD-PTP is linked to MVB formation and endosome maturation, yet how Rab5-GTP elevation is coordinated with early endosome assembly and receptor trafficking is unclear.
• What they did: Mass spectrometry interactomics showed HD-PTP depletion increased Rabaptin5–STRIPAK component association; native IPs and co-expression confirmed STRIPAK–Rabex5-Rabaptin5 links, and co-depletion tested function.
• The result: Strip1 or Rabaptin5 co-depletion with HD-PTP restored early endosome positioning and Rab5 distribution; Strip1 loss reduced central Rab5-positive endosomes and blocked internalised EGF-EGFR accumulation there, while SLMAP loss clustered endosomes and retarded new EGFR endosome generation and EGFR lysosomal transport.

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