TY  - JOUR
ID  - open3253
UR  - http://crdd.osdd.net/open/3253/
IS  - 1
A1  - Paul, Sankalita
A1  - Pant, Rajat
A1  - Sharma, Poonam
A1  - Walia, Kshitiz
A1  - Gupta, Suhasi
A1  - Aseem, Adhil
A1  - Bajwa, Kamlesh Kumari
A1  - George, Ruben
A1  - Varma, Yudish
A1  - Bhatia, Tripta
A1  - Ramachandran, Rajesh
A1  - Tuli, Amit
A1  - Sharma, Mahak
Y1  - 2025/11//
N2  - Small GTP-binding proteins of the Rab, Arf, and Arf-like family mediate the recruitment of their effectors to subcellular membrane-bound compartments, which in turn mediate vesicle budding, motility, and tethering. Here, we report that Tectonin-?-propeller repeat containing protein 2 (TECPR2), a protein mutated in a form of hereditary sensory and autonomic neuropathy (HSAN), is an effector of early endosomal Rab protein, Rab5. We demonstrate that the HSAN-associated missense variants of TECPR2 are defective in Rab5 binding and, consequently, in membrane recruitment. Furthermore, our findings reveal that depletion of TECPR2 impairs recycling of a subset of cargo receptors, including ?5?1 integrins, leading to their lysosomal degradation. TECPR2 interacts with SNX17 and subunits of the WASH complex, molecular players that regulate the formation of actin-dependent cargo retrieval subdomain on the early endosomes. Finally, we show that TECPR2 depletion in zebrafish embryos results in decreased survival, impaired movement and altered neuromuscular synaptic morphology. Our study suggests that TECPR2 functions as a linker between Rab5 and the actin-dependent cargo retrieval machinery, providing insights into how mutations in TECPR2 may result in a neurodegenerative disorder.
PB  - Springer Science and Business Media LLC
JF  - Nat. Commun.
VL  - 16
TI  - The neuropathy-linked protein TECPR2 is a Rab5 effector that regulates cargo recycling from early endosomes
ER  -