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primary topic: The neuropathy-linked protein TECPR2 is a Rab5 effector that regulates cargo recycling from early endosomes

The neuropathy-linked protein TECPR2 is a Rab5 effector that regulates cargo recycling from early endosomes
type: AcademicArticle
type: Article
abstract: 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-β-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 α5β1 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.
date: 2025-11
volume: 16
issue: 1
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

Springer Science and Business Media LLC
type: Organization

Nat. Commun.
type: Collection

Yudish Varma
type: Person
given name: Yudish
family name: Varma

Sankalita Paul
type: Person
given name: Sankalita
family name: Paul

Mahak Sharma
type: Person
given name: Mahak
family name: Sharma

Amit Tuli
type: Person
given name: Amit
family name: Tuli

Tripta Bhatia
type: Person
given name: Tripta
family name: Bhatia

Adhil Aseem
type: Person
given name: Adhil
family name: Aseem

Kshitiz Walia
type: Person
given name: Kshitiz
family name: Walia

Kamlesh Kumari Bajwa
type: Person
given name: Kamlesh Kumari
family name: Bajwa

Rajesh Ramachandran
type: Person
given name: Rajesh
family name: Ramachandran

Poonam Sharma
type: Person
given name: Poonam
family name: Sharma

Suhasi Gupta
type: Person
given name: Suhasi
family name: Gupta

Rajat Pant
type: Person
given name: Rajat
family name: Pant

Ruben George
type: Person
given name: Ruben
family name: George

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primary topic: The neuropathy-linked protein TECPR2 is a Rab5 effector that regulates cargo recycling from early endosomes