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Preparation of Synaptic Plasma Membrane and Postsynaptic Density Proteins Using a Discontinuous Sucrose Gradient
Published on: September 3, 2014
Synaptic adhesion-like molecules (SALMs) promote neurite outgrowth
Philip Y Wang1, Gail K Seabold, Robert J Wenthold
1Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Molecular and Cellular Neurosciences
|July 1, 2008
Summary
All five members of the Seizure-Associated, Leucine-rich repeat, and Amygdala-derived 1 (SALM) protein family promote neurite outgrowth. Their C-terminal PDZ binding domains are crucial for this function in the central nervous system.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Seizure-Associated, Leucine-rich repeat, and Amygdala-derived 1 (SALM) proteins are adhesion molecules predominantly expressed in the central nervous system (CNS).
- Previous studies indicated roles for SALM1 in neurite outgrowth and SALM2 in synapse formation.
Purpose of the Study:
- To comprehensively investigate the role of all five SALM proteins in neurite outgrowth.
- To determine the specific domains of SALMs essential for their function in neuronal development.
Main Methods:
- Expression of epitope-tagged SALM proteins in cultured hippocampal neurons.
- Utilizing antibodies targeting extracellular regions and RNA interference (RNAi) to modulate SALM function.
- Over-expression of deletion constructs and chimeric SALM proteins to identify functional domains.
Main Results:
- SALMs are localized throughout neurons, including axons, dendrites, and growth cones.
- Over-expression of each SALM family member enhanced neurite outgrowth, albeit with distinct phenotypes.
- Antibody-mediated inhibition and RNAi targeting SALMs reduced neurite outgrowth.
- The C-terminal PDZ binding domains of SALMs 1-3 are critical for most neurite outgrowth aspects.
- The N-terminus of SALMs also plays a role in neurite outgrowth, as evidenced by chimera studies.
Conclusions:
- All five SALM proteins actively participate in promoting neurite outgrowth in the CNS.
- Specific domains, particularly the C-terminal PDZ binding sites and the N-terminus, are essential for SALM-mediated neurite extension.
- SALMs represent a significant family of molecules regulating neuronal development and connectivity.
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