Psychiatry related information on MYO5A

• Brain myosin-V is a two-headed unconventional myosin with motor activity [1].

High impact information on MYO5A

• Myosin-V binds to and decorates F-actin, has actin-activated magnesium-ATPase activity, and is a barbed-end-directed motor capable of moving actin filaments at rates of up to 400 nm/s. Myosin-V does not form filaments [1].
• Load-dependent kinetics of myosin-V can explain its high processivity [2].
• Although (18)O exchange and product release measurements favor a mechanism in which actin-activated P(i) release from myosin Va is very rapid, independent of calcium and the tail domain, both heads do not bind actin strongly during steady-state cycling, as assayed by pyrene actin fluorescence [3].
• Binding of myosin-Va to microtubules was saturable and of moderately high affinity (approximately 1:24 Myosin-Va:tubulin; Kd = 70 nM) [4].
• These results demonstrate that myosin-Va is a microtubule binding protein that cross-links and mechanochemically couples microtubules to actin filaments [4].

Biological context of MYO5A

• We demonstrate, via immunoblots, the expression of myosin Va during early stages of embryonic development in chicks, extending from the blastocyst period to the beginning of the fetal period [5].
• Myosin-Va was identified as a microtubule binding protein by cosedimentation analysis in the presence of microtubules [4].
• In transfected mouse melanocytes, expression of the NH(2)-terminal head (catalytic domain) of chick brain myosin-Va codistributed with actin filaments throughout the cytoplasm [6].
• Immunofluorescence cytochemistry demonstrated the localization of myosin V throughout the cytoplasm, in the neurites, growth cone tips, and with an intense asymmetrical perinuclear labeling [7].

Anatomical context of MYO5A

• The expression of myosin Va in specific regions and cellular structures of the nervous system during these early stages was determined by immunocytochemistry using a polyclonal antibody [5].
• These immunolocalization studies indicate temporal and site-specific expression of myosin Va during chick embryo development, suggesting that myosin Va expression is related to recruitment for specific cellular tasks [5].
• We measured the effect of calcium on nucleotide and actin filament binding to full-length myosin Va purified from chick brains [3].
• Our data indicate that the Mg-ATPase cycle of brain myosin-V is tightly regulated by Ca2+, probably via direct binding to the calmodulin light chains in the neck domain, which like brush border myosin-I, results in partial (approximately 30%) dissociation of the calmodulin associated with brain myosin-V [8].
• Compared to conventional myosin from skeletal muscle, brain myosin-V exhibits low K-EDTA- and Ca-ATPase activities (1.8 and 0.8 ATP/s per head) [8].

Associations of MYO5A with chemical compounds

• We demonstrate here that Ca(2+) also induces myosin-Va binding to and cosedimentation with F-actin in the presence of ATP in a similar cooperative manner and calcium concentration range as that observed for the ATPase activity [9].
• Treatment with the microtubule-disrupting drug nocodazole markedly reduces myosin-V staining at the centrosome [6].
• However, vesicles pre-treated with ice-cold 0.1% Triton X-100 supported actin filament motility at rates comparable to those on purified myosin-V [10].
• Time courses of MgmantADP dissociation from myosin V and actomyosin V are biphasic with fast observed rate constants that depend on the [Mg(2+)] and slow observed rate constants that are [Mg(2+)]-independent [11].
• Western blot analyses of PC12 cellular extracts after FGF-2 and/or dibutyryl cAMP treatment revealed variations between myosin V and myosin II expression during neuronal differentiation [7].

Physical interactions of MYO5A

• Thus, because of a number of kinetic adaptations, myosin V is tuned for processive movement on actin and will be capable of transporting cargo at lower motor densities than any other characterized myosin [12].

Other interactions of MYO5A

• Native myosin-Va purified from chick brain, as well as the expressed globular tail domain of this myosin, but not head domain bound to microtubule-associated protein-free microtubules [4].
• In the undifferentiated enterocytes of the intestinal crypts, myosin-VI is expressed but not yet localized to the brush border, in contrast to myosin-V, which does demonstrate an apical distribution in these cells [13].

Analytical, diagnostic and therapeutic context of MYO5A

• Myosin-Va may bind to microtubules via its tail domain because microtubule-bound myosin-Va retained the ability to bind actin filaments resulting in the formation of cross-linked gels of microtubules and actin, as assessed by fluorescence and electron microscopy [4].
• As demonstrated by immunoelectron microscopy, myosin-V associates with 30-40% of the vesicles in this population [10].
• Western blots using affinity purified polyclonal antibodies raised against chicken brain myosin V revealed a component of 190 kDa, a molecular mass typical of myosin V [7].
• Furthermore, Northern blots using a myosin V probe also detected a transcript of around 12 kbp [7].

References