Dataset Information

Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones.

ABSTRACT: A presynaptic adhesion G-protein-coupled receptor, latrophilin-1, and a postsynaptic transmembrane protein, Lasso/teneurin-2, are implicated in trans-synaptic interaction that contributes to synapse formation. Surprisingly, during neuronal development, a substantial proportion of Lasso is released into the intercellular space by regulated proteolysis, potentially precluding its function in synaptogenesis. We found that released Lasso binds to cell-surface latrophilin-1 on axonal growth cones. Using microfluidic devices to create stable gradients of soluble Lasso, we show that it induces axonal attraction, without increasing neurite outgrowth. Using latrophilin-1 knockout in mice, we demonstrate that latrophilin-1 is required for this effect. After binding latrophilin-1, Lasso causes downstream signaling, which leads to an increase in cytosolic calcium and enhanced exocytosis, processes that are known to mediate growth cone steering. These findings reveal a novel mechanism of axonal pathfinding, whereby latrophilin-1 and Lasso mediate both short-range interaction that supports synaptogenesis, and long-range signaling that induces axonal attraction.

SUBMITTER: Vysokov NV

PROVIDER: S-EPMC6245728 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones.

Vysokov Nickolai V NV Silva John-Paul JP Lelianova Vera G VG Suckling Jason J Cassidy John J Blackburn Jennifer K JK Yankova Natalia N Djamgoz Mustafa Ba MB Kozlov Serguei V SV Tonevitsky Alexander G AG Ushkaryov Yuri A YA

eLife 20181120

A presynaptic adhesion G-protein-coupled receptor, latrophilin-1, and a postsynaptic transmembrane protein, Lasso/teneurin-2, are implicated in trans-synaptic interaction that contributes to synapse formation. Surprisingly, during neuronal development, a substantial proportion of Lasso is released into the intercellular space by regulated proteolysis, potentially precluding its function in synaptogenesis. We found that released Lasso binds to cell-surface latrophilin-1 on axonal growth cones. Us ...[more]

PMID: 30457553

Similar Datasets

Project description:To form operative neuronal networks neurons connect to their synaptic partners by axonal outgrowth guided by the movement of the axon tip, a specialized structure known as the growth cone (GC), which travels along stereotypical paths by sensing extracellular guidance cues. Interestingly, GCs contain complex transcriptomes and different guidance cues can rapidly regulate the translation of specific mRNAs which help to remodel the GC cytoskeleton thus steering axon navigation. However, the full landscape of proteomic changes elicited by different cues is not known and the precise protein synthesis (PS)-dependent molecular mechanisms underlying GC repulsive and attractive turning remain largely elusive. Here we have investigated the cue-induced changes in the nascent proteome by pulse Stable Isotope Labeling by Amino acids in Cell culture (pSILAC) in somaless developing retinal axons derived from Xenopus laevis primary cultures. The experimental approach presented major challenges due to the limited quantity of axonal material (~2 μg per condition) and to the desired rapid (5-15 min) time-scale (no previous work has accomplished SILAC with a pulse less than 20 min). To overcome these difficulties we used a superior protocol, termed Single-Pot Solid- Phase-enhanced Sample Preparation, based on ultrasensitive paramagnetic bead technology which allows high proteomic sample recovery from sub-microgram amounts of material. By employing this method we were able to identify up to 500 newly synthesized proteins after only 5 min of pSILAC. Subsequently, we successfully validated the purity and viability of the axonal samples and the reliability of the method. Finally, to characterize and quantify the global patterns of the axonal translational changes in response to specific guidance cues and to unravel the switch between repulsive and attractive responses, we carried out pSILAC in the presence of different repulsive cues and pharmacological reagents that convert repulsion into attraction. Our results uncovered a surprisingly high level of translational activity within the axonal compartment, even in basal conditions. Remarkably, comparative analysis revealed many changes in the nascent proteome in response to different cues, some distinct and some common. Interestingly, several proteins showed cue-specific downregulation. Taken together, our findings suggest a comprehensive GC PS-dependent chemotropic model and novel cue-specific molecular mechanisms possibly underlying the integration of chemotropic responses.

Dataset Information

Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones.

Publications

Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets