Role for cell adhesion and glycosyl (HNK-1 and oligomannoside) recognition in the sharpening of the regenerating retinotectal projection in goldfish

Abstract

Cell‐adhesion molecules (CAMs) are thought to play crucial roles in development and plasticity in the nervous system. This study tested for a role for cell adhesion and in particular, the recognition of two glycosyl epitopes (HNK‐1 and oligomannoside) in the activity‐driven sharpening of the retinotopic map formed by the regenerating retinal fibers of goldfish. HNK‐1 is a prominent glycosyl epitope on many CAMs and extracellular matrix (ECM) molecules, including NCAM, L1, ependymin, and integrins, which have all been implicated in synaptic plasticity. To test for a role of HNK‐1 in the sharpening process, we used osmotic minipumps to infuse HNK‐1 antibodies for 7–21 days into the tectal ventricle starting at 18 days after optic nerve crush. Retinotopic maps recorded at 76–86 days postcrush showed a lack of sharpening similar to that seen previously with two antibodies to ependymin, an HNK‐1–positive ECM component present in cerebrospinal fluid. The multiunit receptive fields at each point averaged 26° versus 11–12° in regenerates infused with control antibodies or Ringer's alone. The HNK‐1 epitope also binds to the G2 domain of laminin to mediate neuron‐ECM adhesion. To test for a role for laminin, a polyclonal antibody was similarly infused and also prevented sharpening to approximately the same degree. The results support a role for the HNK‐1 epitope and laminin in retinotectal sharpening. The oligomannoside epitope (recognized by monoclonal antibody L3) on the CAM L1 interacts with NCAM on the same cell to promote stronger L1 homophilic interactions between cells. Both an L1‐like molecule and NCAM are prominently reexpressed in the regenerating retinotectal system of fish. Infusion of oligomannosidic glycopeptides resulted in decreased sharpening, with multiunit receptive fields that averaged 22.7°. Infusions of mannose‐poor glycopeptides less prominently disrupted sharpening, with average multiunit receptive fields of 18°. Thus, oligomannosidic glycans in particular may play a role in retinotopic sharpening. Blocking glycan‐mediated interactions between CAMs and ECM molecules could decrease the extent of exploratory growth of retinal axon collaterals, preventing them from finding their retinotopic sites, or could interfere with L1 or NCAM and laminin binding at the synaptic densities preventing stabilization of retinotopically appropriate synapses. Together, these results support a prominent role for cell adhesion and glycan epitopes in visual synaptic plasticity. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 659–671, 1998

Peripheral Myelin Protein 22 Is in Complex with α6β4 Integrin, and Its Absence Alters the Schwann Cell Basal Lamina

“…In agreement, the ablation of specific laminin chains alters SC proliferation, which in turn prevents the defasciculation and myelination of peripheral nerves (Colognato et al, 2005). In addition to integrins, laminins bind a variety of adhesive molecules that carry the L2/HNK1 carbohydrate adhesion recognition epitope (Schmidt and Schachner, 1998). PMP22 contains this epitope (Snipes et al, 1993); therefore, it may directly bind laminin.…”

Ependymin, a gene involved in regeneration and neuroplasticity in vertebrates, is overexpressed during regeneration in the echinoderm Holothuria glaberrima

“…N-glysosylation sites are important for the proposed function of ependymin. They can serve as anchorage positions for different oligosaccharides such as glucuronic acid (Shashoua et al, 1986;Schmidt and Schachner, 1998). In addition, it has been suggested that residues of sialic acid attached to the Nglysosylation sites confer the ability to alter ependymin tertiary structure in the presence of calcium and allow its interaction with other ECM components (Ganss and Hoffmann, 1993;Hoffmann and Schwarz, 1996).…”

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

“…Analysis of oligomannoses isolated from synaptosomes showed that the amount of the two major glycans containing five (man5) and eight(man8)mannosesincreasesduringdevelopmentwithman5being the predominant form in adult brain (Fu and Gurd, 1983). Oligomannoses also play a role in long-term potentiation of mouse hippocampal neurons (Lüthl et al, 1994) and in regeneration of retinotectal projections in goldfish (Schmidt and Schachner, 1998).…”