Unconventional myosin-Va is a
motor protein
Motor proteins are a class of molecular motors that can move along the cytoskeleton of cells. They do this by converting chemical energy into mechanical work by the hydrolysis of ATP.
Cellular functions
Motor proteins are the driving force b ...
in charge of the intracellular transport of vesicles, organelles and protein complexes along the actin filaments.
In humans it is coded for by the ''MYO5A''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Structure
In the presence of cargo adapters and calcium, unconventional myosin Va is present in an elongated and active state. It has an N-terminal head domain and a C-terminal tail domain. The actin-binding head (N-Terminal) is an ATP-dependent motor domain that transmits changes from the active site to the light chain lever arm. The C-terminal globular domain (GB) decides the Myosin class and moderate the cargo transport. Also, the GB interacts with other cargo specific proteins. Myosin Va is highly expressed in neurons and melanocytes.
Interactions
MYO5A has been shown to
interact with
DYNLL1
Dynein light chain 1, cytoplasmic is a protein that in humans is encoded by the ''DYNLL1'' gene.
Function
Cytoplasmic dyneins are large enzyme complexes with a molecular mass of about 1,200 kD. They contain two force-producing heads formed pri ...
,
,
DYNLL2
Dynein light chain 2, cytoplasmic is a protein that in humans is encoded by the ''DYNLL2'' gene.
Interactions
DYNLL2 has been shown to interact with DLG4, C12orf40, DLGAP1
Disks large-associated protein 1 (DAP-1), also known as guanylate ...
,
RPGRIP1L,
and
Rab3A
Ras-related protein Rab-3A is a protein that in humans is encoded by the ''RAB3A'' gene. It is involved in calcium-triggered exocytosis in neurons.
Interactions
RAB3A has been shown to interact with:
* RIMS1,
*UNC13A
Unc-13 homolog A ('' ...
.
Clinical significance
* Defects in Myosin Va are associated with
Griscelli syndrome type 1, also known as
Elejalde syndrome
Elejalde syndrome or neuroectodermal melanolysosomal disease is an extremely rare autosomal recessive syndrome (only around 10 cases known) consisting of moderate pigment dilution, profound central nervous system dysfunction, no immune defects, ...
a rare autosomal recessive disorder. This defect is due a mutation in which a premature stop codon in the globular tail disrupt
melanosome
A melanosome is an organelle found in animal cells and is the site for synthesis, storage and transport of melanin, the most common light-absorbing pigment found in the animal kingdom. Melanosomes are responsible for color and photoprotectio ...
transport producing partial albinism.
Griscelli syndrome type 1 can present with pigment defects and neurological disorders such as,
hypotonia
Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...
, motor development delay and mental impairment.
* Myosin Va is highly expressed in the nervous system and it is present in almost the entire brain. MY5A perform an important role in the regulation of axonal vesicle transport on the
neurofilament
Neurofilaments (NF) are classed as Intermediate filament#Type IV, type IV intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring 10 nm in diameter and many micrometers in length. Together with mic ...
s.
The GB of MYO5A can form a complex with Rab3A. The involvement of this complex is important for the
synaptic vesicle
In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are exocytosis, released at the chemical synapse, synapse. The release is regulated by a voltage-dependent calcium channel. Vesicle (biology), Ves ...
s (SVs) trafficking of
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
s and the dynamics of the SVs on the actin filaments.
The absence of MYO5A in the brain can be associated with loco motor dysfunction and neuroendocrine abnormalities. As mention MYO5A is highly expressed on the neurons. Therefore, a mutation on MYO5A can be related with abnormal neuronal development and the progression of
neurodegeneration
A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their cell death, death. Neurodegenerative diseases include amyotrophic lateral sc ...
.
* MYO5A and
MYO5B
Myosin-Vb, a myosin V type protein, is encoded by the ''MYO5B'' gene in humans.
Recent evidence suggests that Myosin-Vb is related to the creation of memories by actin-dependent trafficking of AMPA receptor containing recycling endosomes in den ...
are involved with Kv1.5 (encoded by Potassium voltage-gated channel subfamily A member 5,
KCNA5
Potassium voltage-gated channel, shaker-related subfamily, member 5, also known as KCNA5 or Kv1.5, is a protein that in humans is encoded by the ''KCNA5'' gene.
Function
Potassium channels represent the most complex class of voltage-gated ion ...
) in the myocytes. Kv1.5 is associated with the regulation of the action potential in the myocytes. New strategies targeting Kv1.5 current through MYO5A and MYO5B in human
atrial fibrillation
Atrial fibrillation (AF, AFib or A-fib) is an Heart arrhythmia, abnormal heart rhythm (arrhythmia) characterized by fibrillation, rapid and irregular beating of the Atrium (heart), atrial chambers of the heart. It often begins as short periods ...
(AF) are being studied.
See also
*
Myosin
Myosins () are a Protein family, family of motor proteins (though most often protein complexes) best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are adenosine triphosphate, ATP- ...
*
MYP5B
References
Further reading
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External links
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{{Cytoskeletal proteins
Genes mutated in mice