Kidins220/ARMS regulates Rac1-dependent neurite outgrowth by direct interaction with the RhoGEF Trio

International audienceNeurite extension depends on extracellular signals that lead to changes in gene expression and rearrangement of the actin cytoskeleton. A factor that might orchestrate these signalling pathways with cytoskeletal elements is the integral membrane protein Kidins220/ARMS, a downstream target of neurotrophins. Here, we identified Trio, a RhoGEF for Rac1, RhoG and RhoA, which is involved in neurite outgrowth and axon guidance, as a binding partner of Kidins220. This interaction is direct and occurs between the N-terminus of Trio and the ankyrin repeats of Kidins220. Trio and Kidins220 colocalise at the tips of neurites in NGF-differentiated PC12 cells, where F-actin and Rac1 also accumulate. Expression of the ankyrin repeats of Kidins220 in PC12 cells inhibits NGF-dependent and Trio-induced neurite outgrowth. Similar results are seen in primary hippocampal neurons. Our data indicate that Kidins220 might localise Trio to specific membrane sites and regulate its activity, leading to Rac1 activation and neurite outgrowth

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points