TC10 on endosomes regulates the local balance between microtubule stability and dynamics through the PAK2-JNK pathway and promotes axon outgrowth

• DOI: 10.1242/jcs.263636
• Publication Date: 2025-02-24T15:02:36Z
• Authors: Shingo Koinuma; Misa Miyaji; Suzuka Akiyama; Yasuyuki Ito; Hiroshi Takemura; Naoyuki Wada; Michihiro Igarashi; Takeshi Nakamura
• Keywords: Microtubule-associated protein

The neuronal cytoskeleton comprises microtubules, actin filaments, and neurofilaments plays a critical role in axon outgrowth transport. Microtubules filaments have attracted considerable attention regeneration studies. We previously shown that TC10, Rho family GTPase promotes through membrane addition, is required for efficient regeneration. This study demonstrates TC10 on recycling endosomes, but not the plasma membrane, balances microtubule stability/dynamics axons, thereby counteracting retraction. ablation reduced phosphorylation of SCG10 MAP1B, which are microtubule-binding proteins JNK substrates. Consistently, was decreased knockout neurons than wild-type neurons. Further, deletion significantly PAK2 autophosphorylation. found Rab11-positive endosomes cell bodies its localization to by loss. PAK inhibition tubulin acetylation axons. Furthermore, MKK4/MKK7 mediate signaling from TC10-activated JIP1-positive endosomes. Overall, transmits microtubule-regulatory signal SCG10/MAP1B via axonal