Kinesin-related Smy1 enhances the Rab-dependent association of myosin-V with secretory cargo

Lwin, Kyaw Myo; Li, Donghao; Bretscher, Anthony

doi:10.1091/mbc.e16-03-0185

Cited by 14 publications

(16 citation statements)

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“…A plausible explanation might be that these cargo adaptors contain multiple Myo2-binding sites. Consistently with this explanation, the central coiled-coil region of Smy1 was also reported to bind with Myo2 (24). Although the Inp2-binding site was mapped onto subdomain-I of Myo2-GTD in our work (Fig.…”

Section: Discussionsupporting

confidence: 87%

“…Smy1 was first reported to be a kinesin-like protein, which suppresses a temperature-sensitive phenotype of cells carrying a motility-deficient mutation in Myo2 (22,28). By interacting with both actin and Myo2, Smy1 enhances the motility of Myo2 (29) and cooperates with Sec4 in transporting secretory vesicles (24). The Myo2-interacting site (MIS) in Smy1 was mapped onto its C-terminal region (25) ( Fig.…”

Section: Smy1 Occupies a Hydrophobic Groove In Myo2-gtdmentioning

confidence: 99%

“…So far, a dozen cargo adaptors have been well characterized to directly interact with Myo2-GTD in cargo loading and transport, including mitochondria receptor Myo2 receptor-related protein 1 (Mmr1) (12,13), vacuole-related protein Vac17 (14,15), inheritance of peroxisomes gene 2 (Inp2) (16 -18), and also as Rab GTPase family proteins, Sec4, Ypt32, and Ypt11 (19 -21). Additionally, a kinesin-like protein Smy1 (suppressor of myosin) was shown to bind with Myo2-GTD and cooperate with Sec4 in the secretory vesicle transport (22)(23)(24)(25).…”

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confidence: 99%

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Structural mechanism for versatile cargo recognition by the yeast class V myosin Myo2

Tang

et al. 2019

Journal of Biological Chemistry

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Edited by Wolfgang PetiClass V myosins are actin-dependent motors, which recognize numerous cellular cargos mainly via the C-terminal globular tail domain (GTD). Myo2, a yeast class V myosin, can transport a broad range of organelles. However, little is known about the capacity of Myo2-GTD to recognize such a diverse array of cargos specifically at the molecular level. Here, we solved crystal structures of Myo2-GTD (at 1.9 -3.1 Å resolutions) in complex with three cargo adaptor proteins: Smy1 (for polarization of secretory vesicles), Inp2 (for peroxisome transport), and Mmr1 (for mitochondria transport). The structures of Smy1-and Inp2bound Myo2-GTD, along with site-directed mutagenesis experiments, revealed a binding site in subdomain-I having a hydrophobic groove with high flexibility enabling Myo2-GTD to accommodate different protein sequences. The Myo2-GTD-Mmr1 complex structure confirmed and complemented a previously identified mitochondrion/vacuole-specific binding region. Moreover, differences between the conformations and locations of cargo-binding sites identified here for Myo2 and those reported for mammalian MyoVA (MyoVA) suggest that class V myosins potentially have co-evolved with their specific cargos. Our structural and biochemical analysis not only uncovers a molecular mechanism that explains the diverse cargo recognition by Myo2-GTD, but also provides structural information useful for future functional studies of class V myosins in cargo transport.Class V myosins have long been recognized as key molecular motors involved in intracellular transport along actin filaments. Mammals contain three class V myosins, MyoVa/b/c, whereas the budding yeast Saccharomyces cerevisiae has two, Myo2 and

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Section: Discussionsupporting

confidence: 87%

Section: Smy1 Occupies a Hydrophobic Groove In Myo2-gtdmentioning

confidence: 99%

mentioning

confidence: 99%

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Structural mechanism for versatile cargo recognition by the yeast class V myosin Myo2

Tang

et al. 2019

Journal of Biological Chemistry

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“…An essential function of the yeast myosin-V motor encoded by MYO2 is to transport secretory vesicles to the site of cell growth (Johnston et al, 1991;Schott et al, 1999). The kinesin-related protein Smy1 functions with Myo2 to enhance the association of Myo2 with its receptor on secretory vesicles, the Rab Sec4 (Beningo et al, 2000;Lillie and Brown, 1994;Lwin et al, 2016). We have described myo2 mutant alleles partially compromised in binding Sec4 in which SMY1 becomes essential and used these alleles to generate myo2 smy1 conditional mutations ( Figure 1A and B).…”

Section: Resultsmentioning

confidence: 99%

“…The transport of secretory vesicles by Myo2 is an essential process which has been shown genetically to involve the non-essential kinesin-related protein Smy1 Brown, 1994, 1992). Smy1 interacts directly with Myo2, and we have previously shown that it functions to specifically enhance the association of Myo2 with the secretory vesicle receptor, Sec4 (Lwin et al, 2016;Lillie and Brown, 1994). In this report, we employ a genetic approach to uncover additional components that may be involved in the direct or indirect regulation of secretory vesicle transport.…”

Section: Introductionmentioning

confidence: 99%

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology

Gingras

Lwin

Miller

et al. 2020

Preprint

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Polarized growth requires the integration of polarity pathways with the delivery of exocytic vesicles for cell expansion and counterbalancing endocytic uptake. In budding yeast, the myosin-V Myo2 is aided by the kinesin-related protein Smy1 in carrying out the essential Sec4dependent transport of secretory vesicles to sites of polarized growth. Over-expression suppressors of a conditional myo2 smy1 mutant identified a novel F-BAR-containing RhoGAP, Rgd3, that has activity primarily on Rho3, but also Cdc42. Internally tagged Rho3 is restricted to the plasma membrane in a gradient corresponding to cell polarity that is altered upon Rgd3 overexpression. Rgd3 itself is localized to dynamic polarized vesicles that, while distinct from constitutive secretory vesicles, are dependent on actin and Myo2 function. In vitro Rgd3 associates with liposomes in a PIP2-enhanced manner. Further, the Rgd3 C-terminal region contains several phosphorylatable residues within a reported SH3-binding motif. An unphosphorylated mimetic construct is active and highly polarized, while the phospho-mimetic form is not. Rgd3 is capable of activating Myo2, dependent on its phospho-state and Rgd3 overexpression rescues aberrant Rho3 localization and cell morphologies seen at the restrictive temperature in the myo2 smy1 mutant. We propose a model where Rgd3 functions to modulate and maintain Rho3 polarity during growth.

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Molecular Motors: Subdomain Dynamics and Mechanochemistry

Singh

2020

Frontiers in Protein Structure, Function, and Dynamics

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Kinesin-related Smy1 enhances the Rab-dependent association of myosin-V with secretory cargo

Cited by 14 publications

References 45 publications

Structural mechanism for versatile cargo recognition by the yeast class V myosin Myo2

Structural mechanism for versatile cargo recognition by the yeast class V myosin Myo2

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology

Molecular Motors: Subdomain Dynamics and Mechanochemistry

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