Tetraspanin1 promotes NGF signaling by controlling TrkA receptor proteostasis.

Tetraspanin1 promotes NGF signaling by controlling TrkA receptor proteostasis. Cell Mol Life Sci. 2019 Aug 22;: Authors: Ferrero Restelli F, Fontanet PA, De Vincenti AP, Falzone TL, Ledda F, Paratcha G Abstract The molecular mechanisms that control the biosynthetic trafficking, surface delivery, and degradation of TrkA receptor are essential for proper nerve growth factor (NGF) function, and remain poorly understood. Here, we identify Tetraspanin1 (Tspan1) as a critical regulator of TrkA signaling and neuronal differentiation induced by NGF. Tspan1 is expressed by developing TrkA-positive dorsal root ganglion (DRG) neurons and its downregulation in sensory neurons inhibits NGF-mediated axonal growth. In addition, our data demonstrate that Tspan1 forms a molecular complex with the immature form of TrkA localized in the endoplasmic reticulum (ER). Finally, knockdown of Tspan1 reduces the surface levels of TrkA by promoting its preferential sorting towards the autophagy/lysosomal degradation pathway. Together, these data establish a novel homeostatic role of Tspan1, coordinating the biosynthetic trafficking and degradation of TrkA, regardless the presence of NGF. PMID: 31440771 [PubMed - as supplied by publisher]
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research