Neural cell adhesion molecule is endocytosed via a clathrin-dependent pathway (original) (raw)
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The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998
Cell-cell interactions mediated via cell adhesion molecules (CAMs) are dynamically regulated during nervous system development. One mechanism to control the amount of cell surface CAMs is to regulate their recycling from the plasma membrane. The L1 subfamily of CAMs has a highly conserved cytoplasmic domain that contains a tyrosine, followed by the alternatively spliced RSLE (Arg-Ser-Leu-Glu) sequence. The resulting sequence of YRSL conforms to a tyrosine-based sorting signal that mediates clathrin-dependent endocytosis of signal-bearing proteins. The present study shows that L1 associates in rat brain with AP-2, a clathrin adaptor that captures plasma membrane proteins with tyrosine-based signals for endocytosis by coated pits. In vitro assays demonstrate that this interaction occurs via the YRSL sequence of L1 and the mu 2 chain of AP-2. In L1-transfected 3T3 cells, L1 endocytosis is blocked by dominant-negative dynamin that specifically disrupts clathrin-mediated internalization....
The neural cell adhesion molecule (NCAM) in development and plasticity of the nervous system
Experimental Gerontology, 1998
The neural cell adhesion molecule (NCAM) is a member of the immunoglobulin superfamily and is strongly expressed in the nervous system. NCAM is found in three major forms, of which two-NCAM-140 and NCAM-180 -are transmembrane proteins, while the third-NCAM-120 -is attached to the membrane via a glycosylphosphatidyl inositol anchor. In addition, soluble NCAM forms exist in brain, cerebrospinal fluid, and plasma. NCAM mediates cell adhesion through homophilic as well as through heterophilic interactions. Following NCAM binding, transmembrane signalling is believed to be activated, resulting in increased intracellular calcium. By mediating cell adhesion to other cells and to the extracellular matrix and by activating intracellular signaling pathways, NCAM influences cell migration, neurite extension, and fasciculation, and possibly formation of synapses in the brain. From studies on NCAM knock-out mice, NCAM have been shown to be crucial for the formation of the olfactory bulb and the mossy fiber system in the hippocampus. In addition, NCAM is important for neuronal plasticity in the adult brain associated with learning and regeneration.
Glia, 1998
Neural cell adhesion molecules (NCAMs) constitute a group of cell surface glycoproteins that control cell-cell interactions and play important morphoregulatory roles in the developing and regenerating nervous system. NCAMs exist in a variety of isoforms differing in the cytoplasmic domain and/or their content in sialic acid. The highly sialylated form (PSA-NCAM) is expressed by neurons, whereas it is believed that the less sialylated NCAM forms are synthesised by astrocytes. Moreover, little is known about the molecular sequence of the events that contribute to its expression at the cell surface. Here we report that during the proliferation of cortical astrocytes, at 4 days in primary culture, these cells expressed PSA-NCAM as well as NCAM 180. Then, during cell differentiation these isoforms progressively disappeared and the NCAM 140 became predominant. By immunofluorescence and immunocytochemistry studies we also show that PSA-NCAM and NCAM are first observed in small cytoplasmic spots or vesicles, located in or near the Golgi apparatus, as demonstrated by their co-localization with labelled wheat germ agglutinin (WGA) in this cell organelle. Thereafter, immunostained cytoplasmic NCAM gradually disappeared and became detectable at the cell surface of differentiating astrocytes. We also describe for the first time sialyltransferase activity in these cells and report that the levels of this activity correlated with the decrease in PSA-NCAM expression during the differentiation of astrocytes. These results will contribute to our understanding of the PSA and NCAM intracellular transport pathways and their expression at the cell surface. Moreover, the presence of PSA-NCAM in astrocytes suggests their possible role in nerve branching, fasciculation, and synaptic plasticity.
Cell adhesion molecules in the central nervous system
Cell adhesion & migration
Cell-cell adhesion molecules play key roles at the intercellular junctions of a wide variety of cells, including interneuronal synapses and neuron-glia contacts. Functional studies suggest that adhesion molecules are implicated in many aspects of neural network formation, such as axon-guidance, synapse formation, regulation of synaptic structure and astrocyte-synapse contacts. Some basic cell biological aspects of the assembly of junctional complexes of neurons and glial cells resemble those of epithelial cells. However, the neuron specific junctional machineries are required to exert neuronal functions, such as synaptic transmission and plasticity. In this review, we describe the distribution and function of cell adhesion molecules at synapses and at contacts between synapses and astrocytes.
Neuroscience research, 1993
The neural cell adhesion molecule (NCAM) is a cell surface glycoprotein which is thought to mediate cell adhesion and recognition. During developmental stages, NCAM is highly polysialylated (NCAM-H) by a unique a-2,8-1inked polysialic acid chain (PSA), and this PSA portion of NCAM-H has been found to be closely associated with various developmental processes of the nervous system. Further, recent immunohistochemical investigations have revealed that even in the adult nervous system, a persistent PSA expression has been found confined to several regions: the olfactory bulb, the piriform cortex, the hippocampal dentate gyrus, the hypothalamus, some nuclei of the medulla and the dorsal horn of the spinal cord, which are related directly or indirectly to sensory systems. Moreover, in the dentate gyrus and olfactory bulb the expression is connected with adult neurogenesis that may add new neuronal circuits to the adult neural tissue. Therefore, the possible role of NCAM-H in the central nervous system may be associated not only with neural development, but also with adult functions, such as the processing system of sensory information and neuronal plasticity.
NCAM2/OCAM/RNCAM: Cell adhesion molecule with a role in neuronal compartmentalization
The International Journal of Biochemistry & Cell Biology, 2012
Neural cell adhesion molecules 2 (NCAM2/OCAM/RNCAM), is a paralog of NCAM1. The protein exists in a transmembrane and a lipid-anchored isoform, and has an ectodomain consisting of five immunoglobulin modules and two fibronectin type 3 homology modules. Structural models of the NCAM2 ectodomain reveal that it facilitates cell adhesion through reciprocal interactions between the membrane-distal immunoglobulin modules. There are no known heterophilic NCAM2 binding partners, and NCAM2 is not glycosylated with polysialic acid, a posttranslational modification known to be a major modulator of NCAM1-mediated processes. This suggests that NCAM2 has a function or mode of action distinctly different from that of NCAM1. NCAM2 is primarily expressed in the brain, where it is believed to stimulate neurite outgrowth and to facilitate dendritic and axonal compartmentalization.
Neural cell adhesion molecules in brain plasticity and disease
Multiple sclerosis and related disorders, 2013
Neural cell adhesion molecule (NCAM) has been studied extensively. But it is only in recent times that interest in this molecule has shifted to conditions such as Alzheimer's disease, Multiple Sclerosis and Schizophrenia, focusing on its role in neurodegeneration and abnormal neurodevelopment. NCAM is important in neurite outgrowth, long-term potentiation in the hippocampus and synaptic plasticity. Reduced as well as increased levels in NCAM have been linked to pathology in the brain suggesting that a shift in the equilibrium may be the key. Hence, increasing our understanding of the role of NCAM in health and disease should clear some of the ambiguity surrounding the molecule and even lead to newer potential therapeutic targets. This review consolidates our current understanding of NCAM, focusing on the consequences of dysregulation, its role in neurodegenerative and neurodevelopmental disorders, and the future of NCAM plus potential options for therapy.
Journal of Biological Chemistry, 2004
Molecular force measurements quantified the impact of polysialylation on the adhesive properties both of membrane-bound neural cell adhesion molecule (NCAM) and of other proteins on the same membrane. These results show quantitatively that NCAM polysialylation increases the range and magnitude of intermembrane repulsion. The repulsion is sufficient to overwhelm both homophilic NCAM and cadherin attraction at physiological ionic strength, and it abrogates the protein-mediated intermembrane adhesion. The steric repulsion is ionic strength dependent and decreases substantially at high monovalent salt concentrations with a concomitant increase in the intermembrane attraction. The magnitude of the repulsion also depends on the amount of polysialic acid (PSA) on the membranes, and the PSA-dependent attenuation of cadherin adhesion increases with increasing PSA-NCAM:cadherin ratios. These findings agree qualitatively with independent reports based on cell adhesion studies and reveal the likely molecular mechanism by which NCAM polysialylation regulates cell adhesion and intermembrane space.
The EMBO …, 1994
Department of Morphology, University of Geneva Medical School, 1 rue Michel Servet, CH-1211 Geneva 4, 2Laboratoire de Genetique et Physiologie du Developpement, CNRS 9943, Parc Scientifique de Luminy, Case 907, F-13288 Marseille Cedex 9, France and 3Division of ...