Cargo Release from Myosin V Requires the Convergence of Parallel Pathways that Phosphorylate and Ubiquitylate the Cargo Adaptor

Wong, Sara; Hepowit, Nathaniel L.; Port, Sarah A.; Yau, Richard G.; Peng, Yutian; Azad, Nadia; Habib, Alim; Harpaz, Nofar; Schuldiner, Maya; Hughson, Frederick M.; MacGurn, Jason A.; Weisman, Lois S.

doi:10.1016/j.cub.2020.08.062

Cited by 13 publications

(11 citation statements)

References 66 publications

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“…Adaptors may also play roles unrelated to transport. For example, phosphorylation and ubiquitin-mediated degradation of the yeast vacuolar adaptor Vps17 is required to release the organelle from Myo2 ( Wong et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

The type V myosin-containing complex HUM is a RAB11 effector powering movement of secretory vesicles

et al. 2022

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Section: Discussionmentioning

confidence: 99%

The type V myosin-containing complex HUM is a RAB11 effector powering movement of secretory vesicles

et al. 2022

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“…Adaptors may play additional roles unrelated to transport itself. Notably, they may help to release the vesicle from myosin-5 upon arrival to destination: Phosphorylation and ubiquitin-mediated degradation of the yeast vacuolar adaptor Vps17 is required to release the organelle from Myo2 (Wong et al, 2020). We cannot rule out that UDS1 and HMSV play additional roles, such as retaining SVs in the SPK/vesicle supply center.…”

Section: Discussionmentioning

confidence: 99%

A novel RAB11-containing adaptor complex anchoring myosin-5 to secretory vesicles

Pinar¹,

Alonso²,

Rı́os

et al. 2021

Preprint

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Hyphal fungi grow rapidly by apical extension, providing a notorious example of polarized growth. The continuous supply of secretory vesicles necessary to meet the demands of the extending tip and the long intracellular distances existing between the tip and the basal septum, often localized > 100 μm away from the former, impose the need of efficient networks of intracellular traffic involving exquisite cooperation between microtubule- and actin-mediated transport. In Aspergillus nidulans kinesin-1 conveys secretory vesicles to the hyphal tip, where they are transferred to myosin-5, which focuses them at the growing apex, thereby determining cell shape. This relay mechanism and the central role played by myosin-5 in hyphal morphogenesis suggested that the mechanisms anchoring secretory vesicles to this motor should involve specific adaptor(s) ensuring the robustness of actomyosin-dependent transport. Secretory vesicles are charged with RAB11, a regulatory GTPase that determines the Golgi to post-Golgi identity transition. By using a combination of shotgun proteomics, GST-RAB pull-down assays, in vitro reconstitution experiments, targeted reverse genetics and multidimensional fluorescence microscopy with endogenously tagged proteins we show that RAB11, the master regulator of fungal exocytosis, mediates myosin-5 engagement both by contacting the motor and by recruiting UDS1, a homologue of an as yet uncharacterized Schizosaccharomyces protein 'upregulated during mitosis', which we demonstrate to be a novel RAB11 effector. Analytical ultracentrifugation determined that UDS1 is an elongated dimer and negative-stain electron microscopy showed that, in agreement, UDS1 is rod-shaped. UDS1 does not contact myosin-5 directly, but rather recruits the coiled-coil HMSV, which bridges RAB11/UDS1 to myosin-5. An HMSV-scaffolded complex containing UDS1 and myosin-5 is present in cells, and a RAB11-UDS1-HMSV complex can be reconstituted in vitro in a RAB nucleotide state-dependent manner. In the absence of UDS1/HMSV the steady state levels of myosin-5 at the apical vesicle supply center diminish markedly, such that microtubule-dependent transport spreading vesicles across the apical dome predominates over apex-focused actin-mediated transport. As a consequence, RAB11 and chitin-synthase B (a cargo of the RAB11 pathway) are not focused at the apex, being distributed instead across the apical dome. Therefore, the RAB11 effector UDS1/HMSV cooperates with the GTPase to adapt secretory vesicles to myosin-5, which is required for the apical targeting of RAB11 cargoes and thus for the normal morphology of the hyphae.

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“…, 2020 ). Likewise, the Vps41 alone is involved in the regulation of termination of vacuole inheritance ( Wong et al. , 2020 ), further suggesting that assembly–disassembly dynamics of the HOPS complex must exist in vivo.…”

Section: Resultsmentioning

confidence: 99%

“…Vps39 has been reported to act as the guanine nucleotide exchange factor of the Gtr1 GTPase without participation of other HOPS subunits (Binda et al, 2009) and to mediate phosphatidylethanolamine transport to the mitochondria, independent of both HOPS and vCLAMPs (Iadarola et al, 2020). Likewise, the Vps41 alone is involved in the regulation of termination of vacuole inheritance (Wong et al, 2020), further suggesting that assembly-disassembly dynamics of the HOPS complex must exist in vivo.…”

Section: Vps39 Needs To Disengage From Hops To Form Vclampsmentioning

confidence: 99%

Subunit exchange among endolysosomal tethering complexes is linked to contact site formation at the vacuole

Montoro

Duarte

Auffarth

et al. 2021

MBoC

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The hexameric HOPS (homotypic fusion and protein sorting) complex is a conserved tethering complex at the lysosome-like vacuole, where it mediates tethering and promotes all fusion events involving this organelle. The Vps39 subunit of this complex also engages in a membrane contact site between the vacuole and the mitochondria, called vCLAMP. Additionally, four subunits of HOPS are also part of the endosomal CORVET tethering complex. Here, we analyzed the partition of HOPS and CORVET subunits between the different complexes by tracing their localization and function. We find that Vps39 has a specific role in vCLAMP formation beyond tethering, and that vCLAMPs and HOPS compete for the same pool of Vps39. In agreement, we find that the CORVET subunit Vps3 can take the position of Vps39 in HOPS. This endogenous pool of a Vps3-hybrid complex is affected by Vps3 or Vps39 levels, suggesting that HOPS and CORVET assembly is dynamic. Our data shed light on how individual subunits of tethering complexes such as Vps39 can participate in other functions, while maintaining the remaining subcomplex available for its function in tethering and fusion.

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Cargo Release from Myosin V Requires the Convergence of Parallel Pathways that Phosphorylate and Ubiquitylate the Cargo Adaptor

Cited by 13 publications

References 66 publications

The type V myosin-containing complex HUM is a RAB11 effector powering movement of secretory vesicles

The type V myosin-containing complex HUM is a RAB11 effector powering movement of secretory vesicles

A novel RAB11-containing adaptor complex anchoring myosin-5 to secretory vesicles

Subunit exchange among endolysosomal tethering complexes is linked to contact site formation at the vacuole

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