Role of L1CAM for axon sprouting and branching

Abstract

The central nervous system (CNS) has been traditionally considered as an organ that fails to regenerate in response to injury. Indeed, the lesioned CNS faces a number of obstacles during regeneration, including an overall non-permissive environment for axonal regeneration. However, research during the last few decades has identified axon sprouting as an anatomical correlate for the regenerative capability of the CNS to establish new connections. The immunoglobulin superfamily member L1CAM has been shown to promote the capability of neurons for regenerative axon sprouting and to improve behavioral outcomes after CNS injury. Here, we discuss the cell-autonomous role of L1CAM for axon sprouting in experimental rodent injury models and highlight the molecular interactions of L1CAM with ankyrins, ezrin-radixin-moesin proteins and the Sema3A/Neuropilin ligand-receptor complex in the context of axonal branching.

The Spectrin-Actin-Based Periodic Cytoskeleton as a Conserved Nanoscale Scaffold and Ruler of the Neural Stem Cell Lineage

“…Within this CAM family, its first member, L1CAM, is widely expressed in the developing nervous system. It plays vital roles in cell-cell interactions and is essential in axon guidance and fasciculation (Engle, 2010; Schäfer and Frotscher, 2012; Wiencken-Barger et al, 2004), as well as in induction of myelination by glial cells (Barbin et al, 2004; Fields, 2015; Wood et al, 1990). Moreover, L1CAM shares consensus ankyrin-binding domains with neurofascin and is functionally coupled with ankyrin and, thus, the spectrin-actin cytoskeleton in premyelinated axons (Davis and Bennett, 1994; Scotland et al, 1998).…”

“…Given the homophilic and heterophilic binding capability of members of the L1 family (Engle, 2010; Fields, 2015; Scha¨ fer and Frotscher, 2012), it is thus possible that the aligned 1D peri- odic spectrin-actin-based cytoskeleton we found at neuron- neuron and neuron-glia interfaces may be linked to the intercel- lular interactions between L1CAM, neurofascin, and possibly other CAM proteins on a 1D periodic cytoskeletal scaffold.…”

L1 Cell Adhesion Molecule as a Predictor of Disease-Specific Survival and Patterns of Relapse in Endometrial Cancer

“…L1CAM is a neural cell adhesion molecule that plays a physiological role in the development of central nervous system where it promotes neuronal cell migration, differentiation, and axon guidance. 14 In cancer cells, L1CAM promotes cell proliferation, migration, invasion, and metastasis. 15 Its expression is associated with tumor progression in many types of cancer, including colorectal, gastric, renal, and breast cancer.…”

Growth/differentiation factor-15 and its role in peripheral nervous system lesion and regeneration

“…STAT3 has been shown to be not only essential for the survival of spinal motor neurons, but also critical for the expression of IL-6 and LIF (Dominguez et al, 2010;Haas et al, 1999;Ohbayashi et al, 2007). Extracellular matrix molecules and cell adhesion molecules, such as laminin, NCAM, fibronectin and L1 are also necessary for guiding axons to pass the injury site, to enter the distal stumps and finally to reach the targets (Chen et al, 2005;Chen and Strickland, 2003;Chernousov et al, 2008;Parrinello et al, 2010;Hansen et al, 2008;Schäfer and Frotscher, 2012;Schmid and Maness, 2008). …”