Cargo levels control endosomal PI(3)P homeostasis through direct feedback between SNX17 and MTM1

MTM1 depletion in endosomes causes PI(3)P accumulation and mis-segregation, impairing cargo recycling, and SNX17–MTM1 feedback links cargo levels to local PI(3)P homeostasis.

• Why it matters: PI(3)P is a key endosomal identity lipid, but how cells regulate its homeostasis during cargo sorting and recycling remains unclear.
• What they did: Using imaging plus reconstitution, the study shows MTM1 recruitment and activity depend on SNX17 binding, mediated by sorting motifs in MTM1’s C-terminal tail that compete with SNX17-binding cargo motifs.
• The result: Because SNX17 is a PI(3)P effector, the SNX17–MTM1 competitive interaction establishes negative feedback that couples endosomal cargo levels to PI(3)P depletion.

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