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Endosomal control of local protein synthesis in axons

Neurons are morphologically complex cells that rely on highly compartmentalized signaling to coordinate cellular functions. The endocytic pathway is a crucial trafficking route by which neurons integrate, spatially process and tra... ver más

28/02/2026

OSR

1M€

Presupuesto del proyecto: 1M€

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OSPEDALE SAN RAFFAELE SRL No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2019-11-14

ERC-2019-STG: ERC Starting Grant Scope:Objectives

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2 Participantes

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1.50M€ | Lider

CONSTRUCCIONES Y AUXILIAR DE...

1.20M€ | Participante

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Duración del proyecto: 75 meses Fecha Inicio: 2019-11-14
Fecha Fin: 2026-02-28

Líder del proyecto

OSPEDALE SAN RAFFAELE SRL No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Neurons are morphologically complex cells that rely on highly compartmentalized signaling to coordinate cellular functions. The endocytic pathway is a crucial trafficking route by which neurons integrate, spatially process and transfer information. Endosomal trafficking in axons and dendrites ensures that required molecules and signaling complexes are present where and when they are functionally needed thus fulfilling essential roles in neuronal physiology. Our recent work has revealed the presence of mRNAs and ribosomes on endosomes in axons, raising the exciting possibility that these motile organelles also directly modulate the local proteome by controlling de novo protein synthesis. However, the mechanisms by which endosomes regulate mRNA translation in neurons is unknown. Moreover, the roles of endosome-mediated control of protein synthesis in neuronal development and function have not been investigated. Here, we propose to bridge this knowledge gap by elucidating links between the endocytic pathway and local protein synthesis in neurons, focusing on their functional relationship in axons. By combining genome-wide analysis, genetic tools, state-of-the-art imaging techniques and the use of Xenopus and mouse vertebrate models, we plan to address the following fundamental questions: (i) What are the mRNAs associated with endosomes and does endosomal trafficking regulate their axonal localization? (ii) Does the endocytic pathway mediate the selective translation of axonal mRNAs in response to extracellular factors? (iii) What are the endosome-associated RNA-binding proteins, and what is the effect of perturbing these associations on axonal development and maintenance in vivo? (iv) Does impaired endosomal regulation of axonal mRNA localization and translation cause axonopathies? Answering these questions will set strong foundations for this new area of research and can provide a new angle in our comprehension of neuropathies in need of novel therapeutic strategies.

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