Semaphorin-3A is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''SEMA3A''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

The ''SEMA3A'' gene is a member of the

semaphorin Semaphorins are a class of secreted and membrane proteins that were originally identified as axonal growth cone guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric receptor complexes. Semaphorins ...

family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a

Sema domain The Sema domain is a structural domain of semaphorins, which are a large family of secreted and transmembrane proteins, some of which function as repellent signals during axon guidance. Sema domains also occur in the hepatocyte growth factor re ...

. This secreted Semaphorin-3A protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical

dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...

s. In both cases, the protein is vital for normal neuronal pattern development. Semaphorin-3A is secreted by neurons and surrounding tissue to guide migrating cells and

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

s in the developing nervous system. 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. The guidance is critical for the precise formation of neurons and the surrounding vasculature. Guidance cues, such as Sema3A, induce the collapse and paralysis of neuronal growth cones during development of the nervous system. This guidance cue for

s of

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

s is signaled through receptor complexes containing Neuropilin-1 (

NRP1 Neuropilin-1 is a protein that in humans is encoded by the ''NRP1'' gene. In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins. Function NRP1 is a membrane-bound coreceptor to a tyrosine kinase rece ...

) and a co-receptor. One of the first identified intracellular messenger required for the

growth cone A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago Ramó ...

-collapse induced by Sema3A is the CRMP protein called CRMP2. In addition to its role in the nervous system, Sema3A also acts as an inhibitor of angiogenesis, the process by which new blood vessels develop.

Clinical significance

The protein semaphorin-3A is highly expressed in scar tissue after traumatic central nervous system injuries, such as

spinal cord injury A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cor ...

. Semaphorin-3A, and the other class 3

s, contributes to the failure of neuronal regeneration after CNS injury by regulating axonal re-growth, re-myelination, re-vascularisation, and the

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

. Increased expression of semaphorin-3A is associated with

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

. Additionally, the terminal

Schwann cells Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensh ...

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

(ALS) mice (

SOD1 Superoxide dismutase u-Zn'' also known as superoxide dismutase 1 or hSod1 is an enzyme that in humans is encoded by the ''SOD1'' gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis, fam ...

mutant) express semaphorin-3A at fast-fatigable fiber

neuromuscular junctions A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

greater than

wild-type The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "m ...

mice. This expression is greatest pre-symptomatically corresponding to ALS progression in which fast-fatigable fiber denervation precedes clinical symptoms. Because semaphorin-3A is involved in

collapse,

axon pruning Synaptic pruning, a phase in the development of the nervous system, is the process of synapse elimination that occurs between early childhood and the onset of puberty in many mammals, including humans. Pruning starts near the time of birth and con ...

, and repulsion, it potentially holds a causal relationship to synaptic weakening and denervation that precedes

motor neuron A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectl ...

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

in ALS.

References

External links

* * * {{PDB Gallery, geneid=10371

Function

Clinical significance

References

Further reading

External links