Disease relevance of MYO5A

• Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1) [1].
• We demonstrated mRNA and protein expression of myosin Va in 3 mouse melanocyte lines and 1 human melanoma cell line, using RT-PCR and immunoblotting [2].
• CALI of myosin-V in growth cones of chick dorsal root ganglion neurons resulted in rapid filopodial retraction [3].
• Here we characterized the unitary mechanics of three single-headed fragments of myosin V expressed in the baculovirus/insect cell system [4].
• Green fluorescent protein-VP26 foci co-localize with the actin motor myosin V, suggesting that viral capsids travel along nuclear actin filaments using myosin-based directed transport [5].

Psychiatry related information on MYO5A

• Ca(2+)-dependent regulation of the motor activity of myosin V [6].

High impact information on MYO5A

• In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not [7].
• We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients [7].
• Here we provide direct evidence that myosin-V is indeed a processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament [8].
• Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis [9].
• The role of myosin-V, an unconventional myosin, in growth cone dynamics was examined by chromophore-assisted laser inactivation (CALI) [3].

Biological context of MYO5A

• We also show that an identical phenotype can result from the deletion of the MYO5A F-exon, an exon with a tissue-restricted expression pattern [1].
• We report the isolation and sequencing of "myoxin" (MYH12), the human homologue of the mouse dilute gene, and its assignment to human chromosome 15 [10].
• Analysis of the myosin Va (Myo5a) gene of the dop genome showed the presence of a complex rearrangement consisting of a 306-bp inversion associated with 217-bp and 17-bp deletions [11].
• Mlph is proposed to be a modular protein binding the melanosome-associated protein Rab27a, Myosin Va (MyoVa), actin, and microtubule end-binding protein (EB1), via distinct N-terminal Rab27a-binding domain (R27BD), medial MyoVa-binding domain (MBD), and C-terminal actin-binding domain (ABD), respectively [12].
• Here, we identify and characterize the binding site of DLC on myosin Va [13].

Anatomical context of MYO5A

• Interactions of human Myosin Va isoforms, endogenously expressed in human melanocytes, are tightly regulated by the tail domain [14].
• Myosin Va isoforms containing exon F are able to colocalize with and influence melanosome distribution by indirect interaction with rab27a and direct interaction with melanophilin [14].
• Primary human epidermal melanocytes express six endogenous isoforms of the human actin-associated myosin Va motor protein, involved in organelle transport [14].
• This kinesin/myosin-V heteromotor complex allows long-range movement of vesicles within axons and dendrites on microtubules and short-range movement in the dendritic spines and axon terminals on actin filaments [15].
• Myosin-V, a versatile motor for short-range vesicle transport [15].

Associations of MYO5A with chemical compounds

• Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein [16].
• Transient transfection of antisense phosphorothioate oligodeoxynucleotides targeted against myosin Va mRNA reduced expression of myosin Va protein in cultured mouse melan-a melanocytes by over 70 % 20 h after transfection whereas a control (shuffled sequence) oligonucleotide did not [2].
• The myosin V was labeled with bifunctional rhodamine on one of its calmodulin light chains [17].
• We show that butanedione monoxime (BDM), a known inhibitor of muscle myosin II, inhibits nonmuscle myosin II and myosin V adenosine triphosphatases [18].
• We introduced a tetracysteine motif in the upper 50-kDa domain (residues 292-297) of myosin V containing a single IQ domain (MV 1IQ), allowing us to label this site with the fluorescein biarscenical hairpin-binding dye (FlAsH) (MV 1IQ FlAsH) [19].

Physical interactions of MYO5A

• We investigated the effect of DYNLL2 binding on the structure of a myosin Va heavy chain fragment that contains the DYNLL2 binding site and flanking sequence, only parts of which are strongly predicted to form a coiled coil [20].
• This supports the notion that nucleotide-free myosin V is an excellent model for strongly bound myosin and allows us to describe the actin-myosin interface [21].
• Here, we show by reconstitution using purified proteins that Rab27a and Mlph are sufficient to form a transport complex with myosin Va in vitro [22].
• The kinectin-binding domain on the kinesin tail partially overlaps its head-binding domain and the myosin-Va binding domain [23].

Regulatory relationships of MYO5A

• When our data are taken together, they suggest that exon B and its associated DLC2 have a significant effect on the structure of parts of the coiled-coil tail domains and such a way could influence the regulation and cargo-binding function of myosin Va [13].

Other interactions of MYO5A

• Our immunofluorescence and yeast two-hybrid screening studies reveal that Rab27b can form a tripartite complex on the melanosome membrane with Melanophilin, a Rab27a effector, and protein products of Myosin Va transcripts that contain exon F [24].
• Rab27a and its rabphilin-like effector protein, Melanophilin, recruit myosin-Va to melanosomes and appear to serve as the membrane receptor [15].
• Fragments of the human myosin Va tail and the DLC2 isoform were expressed, and their complex formation was analyzed by pull-down assays, gel filtration, and spectroscopic methods [13].
• Myosin Va is associated with discrete vesicle populations in a number of cell types, but little is known of the function of myosin Vb [25].
• Like myosin-Va, the velocity of myosin-IXb remains constant (38.2 +/- 1.2 nm/s) even at single motor/filament densities [26].

Analytical, diagnostic and therapeutic context of MYO5A

• Immunocytochemistry showed 2 types of myosin Va localisation [2].
• Somatic cell hybrid analysis and in situ hybridization place the MYH12 gene on human chromosome 15, at band q21, and extend distally the known region of chromosome 15 linkage homology on mouse chromosome 9 [27].
• Sequences encoding 1,235 bp of the human myosin heavy chain 12 (MYH12) gene have been cloned from a human brain cDNA library by PCR amplification [27].
• Here we use electron microscopy to show that while working, myosin V spans the helical repeat [28].
• This interaction was confirmed by immunoprecipitation, which also demonstrated that BERP could associate with myosin Va, the product of the dilute gene [29].

References