SEMA3A

Semaphorin-3A is a is_associated_with::protein that in humans is encoded by the SEMA3A is_associated_with::gene.

Function
This gene is a member of the is_associated_with::semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a is_associated_with::PSI domain and a is_associated_with::Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical is_associated_with::dendrites. In both cases, the protein is vital for normal neuronal pattern development.

Semaphorin-3A is a secreted protein, or chemorepulser, secreted by surrounding tissues to guide migrating cells and axons in the developing nervous system of an organism which is critical for the precise formation of neurons and vasculature. Semaphorins, which are short range inhibitory proteins that act as axonal growth cone guidance molecules, are synthesized by neurons during axon pathfinding. Repulsive guidance cue semaphorin-3A (Sema3A) is a gene of the semaphorin family and is expressed by motorneurons to control motor axonal pathfinding. Axon pathfinding is the process by which neurons follow very precise paths, sends out axons, and react to specific chemical environments to reach the correct endpoint. During nervous system development, guidance cues, such as Semaphorin-3A induce the collapse and paralysis of neuronal growth cones. This repulsive cue for developing axons are signaled through receptor complexes containing Neuropilin-1 (is_associated_with::NRP1), which is a protein receptor in active neurons.

The first of the CRMP proteins, CRMP2, was identified as an intracellular messenger required for the is_associated_with::growth cone-collapse induced by semaphorin 3A.

Clinical significance
Increased expression of this protein is associated with is_associated_with::schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of is_associated_with::Alzheimer's disease.

Additionally, the terminal is_associated_with::Schwann cells of is_associated_with::ALS mice (is_associated_with::SOD1 mutant) express Sema3A at fast-fatigable fiber is_associated_with::neuromuscular junctions greater than is_associated_with::wild-type mice. This expression is greatest pre-symptomatically corresponding to ALS progression in which fast-fatigable fiber denervation precedes clinical symptoms. Because Sema3A is involved in is_associated_with::growth cone collapse and is_associated_with::axon pruning and repulsion, it potentially holds a causal relationship to synaptic weakening and denervation that precedes is_associated_with::motor neuron is_associated_with::apoptosis in ALS.