A novel family of adhesion-like molecules that interacts with the NMDA receptor (original) (raw)

The leucine-rich repeat superfamily of synaptic adhesion molecules: LRRTMs and Slitrks

Molecules and Cells, 2012

Synapses are asymmetric intercellular junctions connected by multiple synaptic cell adhesion molecules (CAMs). Synaptic CAMs function in various stages of synaptogenesis -the process of synapse creation -encompassing synapse formation, maturation, refinement, plasticity, and elimination. The list of synaptic CAMs has rapidly grown, although their precise functions of most CAMs at synapses remain incomplete. Members of an emerging class of transmembrane proteins containing leucine-rich repeat (LRR) domains have received considerable recent research attention. In this minireview, I discuss recent findings on LRR-containing synaptic CAMs that impact synapse development and circuit formation, focusing on two families of LRR synaptic CAMs: leucine-rich transmembrane proteins (LRRTMs) and Slit and Trk-like family (Slitrks). Their basic biochemical properties, proposed functions at synapses, physiological significances, and open questions are summarized.

SALM Synaptic Cell Adhesion-like Molecules Regulate the Differentiation of Excitatory Synapses

Neuron, 2006

Synaptic cell adhesion molecules (CAMs) are known to play key roles in various aspects of synaptic structures and functions, including early differentiation, maintenance, and plasticity. We herein report the identification of a family of cell adhesion-like molecules termed SALM that interacts with the abundant postsynaptic density (PSD) protein PSD-95. SALM2, a SALM isoform, distributes to excitatory, but not inhibitory, synaptic sites. Overexpression of SALM2 increases the number of excitatory synapses and dendritic spines. Mislocalized expression of SALM2 disrupts excitatory synapses and dendritic spines. Bead-induced direct aggregation of SALM2 results in coclustering of PSD-95 and other postsynaptic proteins, including GKAP and AMPA receptors. Knockdown of SALM2 by RNA interference reduces the number of excitatory synapses and dendritic spines and the frequency, but not amplitude, of miniature excitatory postsynaptic currents. These results suggest that SALM2 is an important regulator of the differentiation of excitatory synapses.

​Synaptic adhesion molecules and excitatory synaptic transmission

Current opinion in neurobiology, 2017

Synaptic adhesion molecules have been extensively studied for their contribution to the regulation of synapse development through trans-synaptic adhesions. However, accumulating evidence increasingly indicates that synaptic adhesion molecules are also involved in the regulation of excitatory synaptic transmission and plasticity, often through direct or close associations with excitatory neurotransmitter receptors. This review summarizes recent results supporting this emerging concept and underlying mechanisms, and addresses its implications.

Organization of central synapses by adhesion molecules

European Journal of Neuroscience, 2010

Synapses are the primary means for transmitting information from one neuron to the next. They are formed during development of the nervous system, and formation of appropriate synapses is crucial for establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies have revealed a diverse and vast assortment of molecules present at the synapse. It is now important to untangle this large array of proteins and determine how it assembles into a functioning unit. Here we focus on recent reports describing how synaptic cell adhesion molecules interact with and organize the pre-and postsynaptic specializations of both excitatory and inhibitory central synapses.

The role of cell adhesion molecules (CAMs) in defining synapse-specific function and plasticity

Animal Cells and Systems, 2013

One neuron receives thousands of inputs through synapses, which contain distinct molecular components and display different properties. It has been a major challenge in neuroscience to understand the development and function of specific synapses. One of the critical molecules involved in shaping synapse-specific properties is the cell adhesion molecule (CAM). Remarkable numbers of studies have shown the importance of cell-cell interaction mediated by various types of CAMs in defining synapse-specific function. Here, we summarize current understanding of CAMs playing a pivotal role in constructing neural circuits and guiding synapse-specific plasticity. Different CAMs localized at specific synapses are discussed in this review.

The resilient synapse: insights from genetic interference of synaptic cell adhesion molecules

Cell and Tissue Research, 2006

Synaptic cell adhesion molecules (SCAMs) are mostly membrane-anchored molecules with extracellular domains that extend into the synaptic cleft. Prototypical SCAMs interact with homologous or heterologous molecules on the surface of adjacent cells, ensuring the precise apposition of pre-and postsynaptic elements. More recent definitions of SCAMs often include molecules involved in axon pathfinding, cell recognition and synaptic differentiation events, making SCAMs functionally and molecularly a highly diverse group. In this review, we summarize the proposed in vivo functions of a large variety of SCAMs. We mainly focus on results obtained from analyses of genetic model organisms, mostly mouse knockout mutants, lacking expression of the respective candidate genes. In contrast to the substantial effect yielded by some knockouts of molecules involved in synaptic vesicle release, no SCAM mutant has been reported thus far that shows a prominently altered structure of the majority of synapses or even lacks synapses altogether. This surprising resilience of synaptic structure might be explained by a high redundancy between different SCAMs, by the assumption that the crucial molecular players in synapse structure have yet to be discovered or by a grand variability in the mechanisms of synapse formation that underlies the diversity of synapses. Whatever the final answer turns out to be, the genetic dissection of the SCAM superfamilies has led to a much better understanding of the different steps required to form, differentiate and modify a synapse.

Synaptic Cell Adhesion Molecules

2012

During development of the nervous system following axon pathfinding, synaptic connections are established between neurons. Specific cell adhesion molecules (CAMs) accumulate at pre-and postsynaptic sites and trigger synaptic differentiation through interactions with intra-and extracellular scaffolds.

Synaptic adhesion-like molecules (SALMs) promote neurite outgrowth

Molecular and Cellular Neuroscience, 2008

SALMs are a family of five adhesion molecules whose expression is largely restricted to the CNS. Initial reports showed that SALM1 functions in neurite outgrowth while SALM2 is involved in synapse formation. To investigate the function of SALMs in detail, we asked if all five are involved in neurite outgrowth. Expression of epitope-tagged proteins in cultured hippocampal neurons showed that SALMs are distributed throughout neurons, including axons, dendrites, and growth cones. Over-expression of each SALM resulted in enhanced neurite outgrowth, but with different phenotypes. Neurite outgrowth could be reduced by applying antibodies targeting the extracellular leucine rich regions of SALMs and with RNAi. Through over-expression of deletion constructs, we found that the C-terminal PDZ binding domains of SALMs 1-3 are required for most aspects of neurite outgrowth. In addition, by using a chimera of SALMs 2 and 4, we found that the Nterminus is also involved in neurite outgrowth.