Brain myosin-V is a two-headed unconventional myosin with motor activity

Cheney, Richard E.; O'Shea, Maura K.; Heuser, John E.; Coelho, Milton V.; Wolenski, Joseph S.; Espreáfico, Enilza Maria; Forscher, Paul; Larson, Roy Edward; Mooseker, Mark S.

doi:10.1016/s0092-8674(05)80080-7

Cited by 393 publications

(81 citation statements)

References 41 publications

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“…Myosin II is found in growth cones and is localized along F-actin bundles throughout the organelle-rich central domain (Rochlin et al, 1995). Myosin V is a twoheaded unconventional myosin that forms dimers but not filaments and can bind membranes via its tail domain (Espreafico et al, 1992;Cheney et al, 1993). Myosin V is expressed in neuronal growth cones (Cheney et al, 1993;Wang et al, 1996) and is concentrated in organelle-rich regions of the growth cones of rodent superior cervical ganglion cells (Evans et al, 1997).…”

Section: The Movement Of Materialsmentioning

confidence: 99%

The clutch hypothesis revisited: Ascribing the roles of actin-associated proteins in filopodial protrusion in the nerve growth cone

Jay

2000

J. Neurobiol.

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Section: The Movement Of Materialsmentioning

confidence: 99%

The clutch hypothesis revisited: Ascribing the roles of actin-associated proteins in filopodial protrusion in the nerve growth cone

Jay

2000

J. Neurobiol.

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“…Single or multiple repeats IQ motif-like sequences have been identified in myosin, kinases, and IQGAP-like and Ras-GEF signaling proteins in Alzheimer disease proteins (3)(4)(5). Tissue myosin V copurify with at least two light chains in addition to calmodulin, but the identity and binding sites of these light chains are unknown (6). It has been shown that either an essential light chain or CaM can occupy the first IQ motif of myosin V (7,8).…”

mentioning

confidence: 99%

Structural Basis for the Interaction of the Myosin Light Chain Mlc1p with the Myosin V Myo2p IQ Motifs

Pennestri

Melino

Contessa

et al. 2007

Journal of Biological Chemistry

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Calmodulin, regulatory, and essential myosin light chain are evolutionary conserved proteins that, by binding to IQ motifs of target proteins, regulate essential intracellular processes among which are efficiency of secretory vesicles release at synapsis, intracellular signaling, and regulation of cell division. The yeast Saccharomyces cerevisiae calmodulin Cmd1 and the essential myosin light chain Mlc1p share the ability to interact with the class V myosin Myo2p and Myo4 and the class II myosin Myo1p. These myosins are required for vesicle, organelle, and mRNA transport, spindle orientation, and cytokinesis. We have used the budding yeast model system to study how calmodulin and essential myosin light chain selectively regulate class V myosin function. NMR structural analysis of uncomplexed Mlc1p and interaction studies with the first three IQ motifs of Myo2p show that the structural similarities between Mlc1p and the other members of the EF-hand superfamily of calmodulin-like proteins are mainly restricted to the C-lobe of these proteins. The N-lobe of Mlc1p presents a significantly compact and stable structure that is maintained both in the free and complexed states. The Mlc1p N-lobe interacts with the IQ motif in a manner that is regulated both by the IQ motifs sequence as well as by light chain structural features. These characteristic allows a distinctive interaction of Mlc1p with the first IQ motif of Myo2p when compared with calmodulin. This finding gives us a novel view of how calmodulin and essential light chain, through a differential binding to IQ1 of class V myosin motor, regulate this activity during vegetative growth and cytokinesis.Myosin V are processive motors that transport a variety of intracellular cargo in a manner that is timely, selectively, and reversibly regulated by its interaction with different proteins via their cargo bound domain (1, 2). Myosin V display a dimeric heavy chain containing several light chain binding sites called IQ motifs. The so-called IQ motif (ϳ23-25 residues), with a consensus sequence of the form IQXXXRGXXXR, is repeated tandemly (2-6 times) in the heavy chain of many myosins. These motifs are among the best known Ca 2ϩ -independent calmodulin (CaM) 3 and myosin light chain targets. Single or multiple repeats IQ motif-like sequences have been identified in myosin, kinases, and IQGAP-like and Ras-GEF signaling proteins in Alzheimer disease proteins (3-5). Tissue myosin V copurify with at least two light chains in addition to calmodulin, but the identity and binding sites of these light chains are unknown (6). It has been shown that either an essential light chain or CaM can occupy the first IQ motif of myosin V (7, 8). How such differential interaction is achieved is unknown. Nor is it clear if and when essential light chain and CaM compete for the same site (4, 9 -11). Recent structural and genetic studies point to a previously uncovered role for calmodulin/myosin light chain interaction with the class V myosin IQ motifs in regulating the cargo binding abiliti...

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“…CaM has four high-affinity calciumbinding sites called EF-hands, each composed of two a-helices connected by a calcium-binding loop. Murine myosin Va isolated from tissue only binds CaM [11], while that isolated from chicken brain contains both CaM and a specific light chain of the essential light chain family (called L17 or L23) [12][13][14]. Based on analysis of proteolytic fragments of myoVa purified from chick brain, it was concluded that the specific light chain does not bind to IQ motif one or two [14].…”

Section: Lever Armmentioning

confidence: 99%

Myosin V from head to tail

Trybus

2008

Cell. Mol. Life Sci.

167

139

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Myosin V (myoV), a processive cargo transporter, has arguably been the most well-studied unconventional myosin of the past decade. Considerable structural information is available for the motor domain, the IQ motifs with bound calmodulin or light chains, and the cargo-binding globular tail, all of which have been crystallized. The repertoire of adapter proteins that link myoV to a particular cargo is becoming better understood, enabling cellular transport processes to be dissected. MyoV is processive, meaning that it takes many steps on actin filaments without dissociating. Its extended lever arm results in long 36-nm steps, making it ideal for single molecule studies of processive movement. In addition, electron microscopy revealed the structure of the inactive, folded conformation of myoV when it is not transporting cargo. This review provides a background on myoV, and highlights recent discoveries that show why myoV will continue to be an active focus of investigation.

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Brain myosin-V is a two-headed unconventional myosin with motor activity

Cited by 393 publications

References 41 publications

The clutch hypothesis revisited: Ascribing the roles of actin-associated proteins in filopodial protrusion in the nerve growth cone

The clutch hypothesis revisited: Ascribing the roles of actin-associated proteins in filopodial protrusion in the nerve growth cone

Structural Basis for the Interaction of the Myosin Light Chain Mlc1p with the Myosin V Myo2p IQ Motifs

Myosin V from head to tail

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