NOG-Derived Peptides Can Restore Neuritogenesis on a CRASH Syndrome Cell Model.

Matteo Gasparotto,Alessandro Grinzato,Elisabetta Bergantino,Francesco Filippini,Yuriko Suemi Hernandez Gomez,Giulia Pontarollo,Daniele Peterle,Giorgia Scapin,Federica Zen,Vincenzo De Filippis,Laura Acquasaliente

doi:10.3390/biomedicines10010102

Matteo Gasparotto, Alessandro Grinzato + Show 9 more

Open Access

https://doi.org/10.3390/biomedicines10010102

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Journal: Biomedicines	Publication Date: Jan 4, 2022
Citations: 3	License type: CC BY 4.0

Affiliation: University of Padua, Harvard University

Abstract

Homo- and heterophilic binding mediated by the immunoglobulin (Ig)-like repeats of cell adhesion molecules play a pivotal role in cell-cell and cell-extracellular matrix interactions. L1CAM is crucial to neuronal differentiation, in both mature and developing nervous systems, and several studies suggest that its functional interactions are mainly mediated by Ig2–Ig2 binding. X-linked mutations in the human L1CAM gene are summarized as L1 diseases, including the most diagnosed CRASH neurodevelopmental syndrome. In silico simulations provided a molecular rationale for CRASH phenotypes resulting from mutations I179S and R184Q in the homophilic binding region of Ig2. A synthetic peptide reproducing such region could both mimic the neuritogenic capacity of L1CAM and rescue neuritogenesis in a cellular model of the CRASH syndrome, where the full L1CAM ectodomain proved ineffective. Presented functional evidence opens the route to the use of L1CAM-derived peptides as biotechnological and therapeutic tools.

Highlights

Introduction published maps and institutional affilDuring development, neurons extend their axons to find the right targets in a complex and changing environment and establish a functional synaptic network
L1-A derives from the NOG motif of L1CAM, and it is suggested to mimic the homophilic binding of its extracellular domain (L1CAM ED) [17]
Such curves are similar to those of L1-A and ROBO2-A reported in Figure 1C,D: both peptides are active in the highnanomolar range and reach plateau at 1 μM

Summary

Introduction

Introduction published maps and institutional affilDuring development, neurons extend their axons to find the right targets in a complex and changing environment and establish a functional synaptic network. Each axon is tipped with the growth cone, a specialized structure with highly dynamic behavior and responsiveness to multiple sources of spatial information, guiding the axon itself toward the right targets with an impressive level of accuracy [1]. Cell adhesion molecules (CAMs) with immunoglobulin (Ig)-like repeats play a fundamental role in cell-cell and cellextracellular matrix (ECM) interactions in both mature and developing nervous systems, as well as in axonal regeneration and neural repair [2]. L1CAM plays an important role in neuronal differentiation: it can induce neuritogenesis, guide axonal growth cones through laminin-induced haptotaxis [4], fasciculation, iations

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