Myosin-Va (MYO5A) is a motor protein in charge of the intracellular transport of vesicles, organelles and protein complexes along the actin filaments. [5] [6] [7] MYO5A gene encodes for the unconventional Myosin motor Va. [8] [9] [10]
Myosin-Va (MYO5A) is a motor protein in charge of the intracellular transport of vesicles, organelles and protein complexes along the actin filaments. [5] [6] [7] MYO5A gene encodes for the unconventional Myosin motor Va. [8] [9] [10]
In the presence of cargo adapters and calcium, Myosin Va is present in an elongated and active state. Myosin V has an N-terminal head domain and a C-terminal tail domain. The actin-binding head (N-Terminal) of Myosin V 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. [5] [6]
MYO5A has been shown to interact with DYNLL1, [11] RAB27A, [12] [13] DYNLL2, [11] [14] RPGRIP1L, [15] Rab3A [6] and miR-145. [16]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Abnormal [18] |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Plasma immunoglobulins | Normal |
| Haematology | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Tail epidermis wholemount | Abnormal |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| Salmonella infection | Abnormal [19] |
| Citrobacter infection | Normal [20] |
| All tests and analysis from [21] [22] |
Model organisms have been used in the study of MYO5A function. A conditional knockout mouse line, called Myo5atm1e(KOMP)Wtsi [23] [24] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. [25] [26] [27]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [21] [28] Twenty five tests were carried out on mutant mice and three significant abnormalities were observed. [21] Male homozygous mutants had abnormal hair cycles, coat colouration and an increased susceptibility to bacterial infection. [21]
Mutations in this gene cause a form of Griscelli syndrome in horses known as "Lavender Foal Syndrome" [29]
Myosins are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The term was originally used to describe a group of similar ATPases found in the cells of both striated muscle tissue and smooth muscle tissue. Following the discovery by Pollard and Korn (1973) of enzymes with myosin-like function in Acanthamoeba castellanii, a global range of divergent myosin genes have been discovered throughout the realm of eukaryotes.
Rab27 is a member of the Rab subfamily of GTPases. Rab27 is post translationally modified by the addition of two geranylgeranyl groups on the two C-terminal cysteines.
Griscelli syndrome is a rare autosomal recessive disorder characterized by albinism (hypopigmentation) with immunodeficiency, that usually causes death by early childhood. Researchers have developed three different classifications of the form of disorder, characterised by different signs and symptoms. Type 1 Griscelli Syndrome is assosciated with severe brain function issues along with distinctive discolouring of the hair and skin. Type 2 Griscelli Syndrome have immune system abnormalities in addition to hypopigmentation of skin and hair. Finally, Type 3 is seen as those only affected by hypopigmentation of the skin and hair. This type is not associated with immune deficiencies or neurological abnormalities.
Myosin VIIA is protein that in humans is encoded by the MYO7A gene. Myosin VIIA is a member of the unconventional myosin superfamily of proteins. Myosins are actin binding molecular motors that use the enzymatic conversion of ATP - ADP + inorganic phosphate (Pi) to provide the energy for movement.
Melanophilin is a carrier protein which in humans is encoded by the MLPH gene. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.
Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.
Myosin VI, also known as MYO6, is a protein. It has been found in humans, mice, fruit flies, and nematodes.
Myosin-9 also known as myosin, heavy chain 9, non-muscle or non-muscle myosin heavy chain IIa (NMMHC-IIA) is a protein which in humans is encoded by the MYH9 gene.
WAS/WASL-interacting protein (WIP) is a protein that in humans is encoded by the WIPF1 gene.
Ras-related protein Rab-8A is a protein that in humans is encoded by the RAB8A gene.
Myosin heavy chain, α isoform (MHC-α) is a protein that in humans is encoded by the MYH6 gene. This isoform is distinct from the ventricular/slow myosin heavy chain isoform, MYH7, referred to as MHC-β. MHC-α isoform is expressed predominantly in human cardiac atria, exhibiting only minor expression in human cardiac ventricles. It is the major protein comprising the cardiac muscle thick filament, and functions in cardiac muscle contraction. Mutations in MYH6 have been associated with late-onset hypertrophic cardiomyopathy, atrial septal defects and sick sinus syndrome.
Myosin-Ic is a protein that in humans is encoded by the MYO1C gene.
Myosin X, also known as MYO10, is a protein that in humans is encoded by the MYO10 gene.
Myosin-Ia is a protein that in humans is encoded by the MYO1A gene.
Myosin-Vb, a myosin V type protein, is encoded by the MYO5B gene in humans.
Myosin IIIA is a protein that in humans is encoded by the MYO3A gene.
Synaptotagmin-like protein 1 is a protein that in humans is encoded by the SYTL1 gene.
Ras-related protein Rab-40A is a protein that in humans is encoded by the RAB40A gene.
Ras-related protein Rab-27A is a protein that in humans is encoded by the RAB27A gene.
Myosin-XV is a protein that in humans is encoded by the MYO15A gene.
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