Mouse Myosin-19 Is a Plus-end-directed, High-duty Ratio Molecular Motor

Lu, Zhenwu; Ma, Xiaonan; Zhang, Hai-Man; Ji, Huan-Hong; Ding, Hao; Zhang, Jie; Luo, Dan; Sun, Yujie; Li, Xiangdong

doi:10.1074/jbc.m114.569087

Cited by 44 publications

(58 citation statements)

References 51 publications

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“…Although there is no current evidence for a role of myosin 19 in mitochondrial fission, some of the studies in the literature (including ours) (Korobova et al, 2014;DuBoff et al, 2012) could have inadvertently inhibited myosin 19 instead of (or in addition to) myosin II, because myosin 19 has the same regulatory light chain (RLC) as myosin II (Lu et al, 2014). However, the effects observed upon suppression of the myosin II heavy chain suggest that the fission effects are indeed specific for myosin II (Korobova et al, 2014).…”

Section: Predicting Possible Routes To Mitochondrial Fissionmentioning

confidence: 60%

Novel roles for actin in mitochondrial fission

Hatch

Gurel

Higgs

2014

Journal of Cell Science

130

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Mitochondrial dynamics, including fusion, fission and translocation, are crucial to cellular homeostasis, with roles in cellular polarity, stress response and apoptosis. Mitochondrial fission has received particular attention, owing to links with several neurodegenerative diseases. A central player in fission is the cytoplasmic dynaminrelated GTPase Drp1, which oligomerizes at the fission site and hydrolyzes GTP to drive membrane ingression. Drp1 recruitment to the outer mitochondrial membrane (OMM) is a key regulatory event, which appears to require a pre-constriction step in which the endoplasmic reticulum (ER) and mitochondrion interact extensively, a process termed ERMD (ER-associated mitochondrial division). It is unclear how ER-mitochondrial contact generates the force required for pre-constriction or why pre-constriction leads to Drp1 recruitment. Recent results, however, show that ERMD might be an actin-based process in mammals that requires the ER-associated formin INF2 upstream of Drp1, and that myosin II and other actinbinding proteins might be involved. In this Commentary, we present a mechanistic model for mitochondrial fission in which actin and myosin contribute in two ways; firstly, by supplying the force for preconstriction and secondly, by serving as a coincidence detector for Drp1 binding. In addition, we discuss the possibility that multiple fission mechanisms exist in mammals.

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Section: Predicting Possible Routes To Mitochondrial Fissionmentioning

confidence: 60%

Novel roles for actin in mitochondrial fission

Hatch

Gurel

Higgs

2014

Journal of Cell Science

130

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“…In vivo , clustering of myosins occurs on the surface of a membrane or a cargo vesicle is required for intracellular transport processes. The tail domain of myosin‐19, a monomeric myosin with a high duty ratio, associates with mitochondria in cells . The myosin‐dependent transport of mitochondria along the cellular actin cytoskeleton requires the presence of multiple myosins on the organelle and is important for the distribution and mitochondrial partitioning during cell division .…”

Section: Kinetic Adaptations Of Myosinsmentioning

confidence: 99%

“…At the same time, the low ATP concentration would trigger an increase in mitochondrial ATP production that in turn could locally increase the ATP concentration in the cytoplasm. The combined action of transport and anchor function of different myosins‐19 on mitochondria could result the mitochondrial network shape and geometry changes observed in cells .…”

Section: Kinetic Adaptations Of Myosinsmentioning

confidence: 99%

Kinetic Adaptations of Myosins for Their Diverse Cellular Functions

Heissler

Sellers

2016

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Members of the myosin superfamily are involved in all aspects of eukaryotic life. Their function ranges from the transport of organelles and cargos to the generation of membrane tension, and the contraction of muscle. The diversity of physiological functions is remarkable, given that all enzymatically active myosins follow a conserved mechanoenzymatic cycle in which the hydrolysis of ATP to ADP and inorganic phosphate is coupled to either actin-based transport or tethering of actin to defined cellular compartments. Kinetic capacities and limitations of a myosin are determined by the extent to with actin can accelerate the hydrolysis of ATP and the release of the hydrolysis products and are indispensably linked to its physiological tasks. This review focuses on kinetic competencies that – together with structural adaptations – result in myosins with unique mechanoenzymatic properties targeted to their diverse cellular function.

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“…MYO19 contains a plus-end directed, actin-activated ATPase [Lu et al 2014] with mechanochemical characteristics suggesting involvement in mitochondrial transport or positioning [Adikes et al 2013]. RNA interference approaches have identified a role for MYO19 in mitochondrial inheritance during mitosis, where depletion of MYO19 leads to asymmetric mitochondrial inheritance into daughter cells, as well as to defects in cytokinesis [Rohn et al 2014].…”

Section: Introductionmentioning

confidence: 99%

Positively charged residues within the MYO19 MyMOMA domain are essential for proper localization of MYO19 to the mitochondrial outer membrane

et al. 2016

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Myosins are well characterized molecular motors essential for intracellular transport. MYO19 copurifies with mitochondria, and can be released from mitochondrial membranes by high pH buffer, suggesting that positively-charged residues participate in interactions between MYO19 and mitochondria. The MYO19-specific mitochondria outer membrane association domain (MyMOMA) contains ~150 amino acids with a pI ~9, and is sufficient for localization to the mitochondrial outer membrane. The minimal sequence and specific residues involved in mitochondrial binding have not been identified. To address this, we generated GFP-MyMOMA truncations, establishing the boundaries for truncations based on sequence homology. We identified an 83-amino acid minimal binding region enriched with basic residues (pI ~ 10.5). We sequentially replaced basic residues in this region with alanine, identifying residues R882 and K883 as essential for mitochondrial localization. Constructs containing the RK882-883AA mutation primarily localized with the endoplasmic reticulum (ER). To determine if ER-associated mutant MyMOMA domain and mitochondria-associated wild type MyMOMA display differences in kinetics of membrane interaction, we paired FRAP analysis with permeabilization activated reduction in fluorescence (PARF) analysis. Mitochondria-bound and ER-bound MYO19 constructs displayed slow dissociation from their target membrane when assayed by PARF; both constructs displayed exchange within their respective organelle networks. However, ER-bound mutant MYO19 displayed more rapid exchange within the ER network than did mitochondria-bound MYO19. Taken together these data indicate that the MyMOMA domain contains strong membrane-binding activity, and membrane targeting is mediated by a specific, basic region of the MYO19 tail with slow dissociation kinetics appropriate for its role(s) in mitochondrial network dynamics.

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Mouse Myosin-19 Is a Plus-end-directed, High-duty Ratio Molecular Motor

Cited by 44 publications

References 51 publications

Novel roles for actin in mitochondrial fission

Novel roles for actin in mitochondrial fission

Kinetic Adaptations of Myosins for Their Diverse Cellular Functions

Positively charged residues within the MYO19 MyMOMA domain are essential for proper localization of MYO19 to the mitochondrial outer membrane

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