 | This article's lead section may be too short to adequately summarize the key points.(September 2021) |
Plexin-A4 is a protein that in humans is encoded by the PLXNA4 gene. [5]
| | This article's lead section may be too short to adequately summarize the key points.(September 2021) |
Plexin-A4 is a protein that in humans is encoded by the PLXNA4 gene. [5]
Plexin A4 binds to neuropilin 1 (Nrp1) and neuropilin 2 (Nrp2) and transduces signals from Sema3A, Sema6A, and Sema6B. [6] These Nrp-plexin and semaphorin complexes initiate cascades that regulate diverse processes such as axon pruning and repulsion, dendritic attraction and branching, regulation of cell migration, vascular remodeling, and growth cone collapse. [7] [8] Both upregulation and downregulation of Plexin A4 has been observed following neural injury suggesting a dynamic role for Sema3A and Plexin A4 in neural maintenance and regeneration. [7] [9] Additionally, Sema3A and therefore its receptor, Plexin A4, have been implicated as possible components of fast-fatigable muscle fiber denervation in ALS. [10]
Plexin A4 has ~1890 amino acids that include a likely signal sequence, transmembrane domain, and 12 extracellular N-linked glycosylation sites. It also contains domains consistent with other class A plexins including a Sema domain, three "Met-related sequences"/cysteine clusters, three extracellular glycine-proline repeats, intracellular SP domains, and a putative intracellular tyrosine kinase phosphorylation site. [11]
In the adult rat central nervous system (CNS), plexin A4 was present in neurons and fibers throughout the brain and spinal cord, including neocortex, hippocampus, lateral hypothalamus, red nucleus, facial nucleus, and the mesencephalic trigeminal nucleus. Fibers expressed Plexin A4 in the lateral septum, nucleus accumbens, several thalamic nuclei, substantia nigra pars reticulata, zona incerta, pontine reticular formation, as well as in several cranial nerve nuclei. [12] Plexin A4 has been found in dorsal and, to a greater extent, ventral horns of the spinal cord. Both motor neurons and interneurons in the ventral horn express Plexin A4. Motor axons exiting via the ventral roots and the ascending and descending white matter tracts express Plexin A4. In dorsal root ganglia, Plexin A4 is expressed in the neuronal cell bodies as well as the central and peripheral processes of those cells. [7]
In neuroanatomy, the optic chiasm, or optic chiasma, is the part of the brain where the optic nerves cross. It is located at the bottom of the brain immediately inferior to the hypothalamus. The optic chiasm is found in all vertebrates, although in cyclostomes, it is located within the brain.
The dorsal column–medial lemniscus pathway (DCML) is a sensory pathway of the central nervous system that conveys sensations of fine touch, vibration, two-point discrimination, and proprioception (position) from the skin and joints. It transmits information from the body to the primary somatosensory cortex in the postcentral gyrus of the parietal lobe of the brain. The pathway receives information from sensory receptors throughout the body, and carries this in nerve tracts in the white matter of the dorsal column of the spinal cord to the medulla, where it is continued in the medial lemniscus, on to the thalamus and relayed from there through the internal capsule and transmitted to the somatosensory cortex. The name dorsal-column medial lemniscus comes from the two structures that carry the sensory information: the dorsal columns of the spinal cord, and the medial lemniscus in the brainstem.
A retinal ganglion cell (RGC) is a type of neuron located near the inner surface of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina amacrine cells. Retina amacrine cells, particularly narrow field cells, are important for creating functional subunits within the ganglion cell layer and making it so that ganglion cells can observe a small dot moving a small distance. Retinal ganglion cells collectively transmit image-forming and non-image forming visual information from the retina in the form of action potential to several regions in the thalamus, hypothalamus, and mesencephalon, or midbrain.
The spinocerebellar tract is a nerve tract originating in the spinal cord and terminating in the same side (ipsilateral) of the cerebellum.
The apex of the posterior grey column, one of the three grey columns of the spinal cord, is capped by a V-shaped or crescentic mass of translucent, gelatinous neuroglia, termed the substantia gelatinosa of Rolando, which contains both neuroglia cells, and small nerve cells. The gelatinous appearance is due to a very low concentration of myelinated fibers. It extends the entire length of the spinal cord and into the medulla oblongata where it becomes the spinal nucleus of the trigeminal nerve.
The posterolateral tract is a small strand situated in relation to the tip of the posterior column close to the entrance of the posterior nerve roots. It is present throughout the spinal cord, and is most developed in the upper cervical regions.
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 are usually cues to deflect axons from inappropriate regions, especially important in the neural system development. The major class of proteins that act as their receptors are called plexins, with neuropilins as their co-receptors in many cases. The main receptors for semaphorins are plexins, which have established roles in regulating Rho-family GTPases. Recent work shows that plexins can also influence R-Ras, which, in turn, can regulate integrins. Such regulation is probably a common feature of semaphorin signalling and contributes substantially to our understanding of semaphorin biology.
Neuropilin is a protein receptor active in neurons.
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 continues into the late-20s. During pruning, both the axon and dendrite decay and die off. It was traditionally considered to be complete by the time of sexual maturation, but this was discounted by MRI studies.
A plexin is a protein which acts as a receptor for semaphorin family signaling proteins. It is classically known for its expression on the surface of axon growth cones and involvement in signal transduction to steer axon growth away from the source of semaphorin. Plexin also has implications in development of other body systems by activating GTPase enzymes to induce a number of intracellular biochemical changes leading to a variety of downstream effects.
Neuropilin 2 (NRP2) is a protein that in humans is encoded by the NRP2 gene.
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.
Semaphorin-3A is a protein that in humans is encoded by the SEMA3A gene.
Semaphorin-4D (SEMA4D) also known as Cluster of Differentiation 100 (CD100), is a protein of the semaphorin family that in humans is encoded by the SEMA4D gene.
Semaphorin-3F is a protein that in humans is encoded by the SEMA3F gene.
Semaphorin-3C is a protein that in humans is encoded by the SEMA3C gene.
Plexin-A1 is a protein that in humans is encoded by the PLXNA1 gene.
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spinal cord, which contains cerebrospinal fluid. The brain and spinal cord together make up the central nervous system (CNS). In humans, the spinal cord begins at the occipital bone, passing through the foramen magnum and then enters the spinal canal at the beginning of the cervical vertebrae. The spinal cord extends down to between the first and second lumbar vertebrae, where it ends. The enclosing bony vertebral column protects the relatively shorter spinal cord. It is around 45 cm (18 in) long in adult men and around 43 cm (17 in) long in adult women. The diameter of the spinal cord ranges from 13 mm in the cervical and lumbar regions to 6.4 mm in the thoracic area.
The growth cone is a highly dynamic structure of the developing neuron, changing directionality in response to different secreted and contact-dependent guidance cues; it navigates through the developing nervous system in search of its target. The migration of the growth cone is mediated through the interaction of numerous trophic and tropic factors; netrins, slits, ephrins and semaphorins are four well-studied tropic cues (Fig.1). The growth cone is capable of modifying its sensitivity to these guidance molecules as it migrates to its target; this sensitivity regulation is an important theme seen throughout development.
Alain Chédotal is a French researcher specialising in the development of neural circuits. He has been a member of the French Academy of sciences since 2017.
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