The role of myosin Va in secretory granule trafficking and exocytosis

Eichler, Tilo Wolf; Kögel, Tanja; Bukoreshtliev, Nickolay V.; Gerdes, Hans‐Hermann

doi:10.1042/bst0340671

Cited by 39 publications

(36 citation statements)

References 42 publications

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“…Even though Myo5a has been implicated in the regulation of secretory vesicle trafficking its interaction with Rab3A had not been established previously. Studies of Myo5a in different cell types shows that this motor is involved in the capture of vesicles and their actin-based transport, as well as in late steps in exocytosis (56). Thus, our results support the idea that GTP-bound Rab3A is involved in Myo5a-dependent vesicle transport.…”

Section: Discussionsupporting

confidence: 80%

Myosin5a Tail Associates Directly with Rab3A-containing Compartments in Neurons

Wöllert

Patel

Lee

et al. 2011

Journal of Biological Chemistry

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Myosin-Va (Myo5a) is a motor protein associated with synaptic vesicles (SVs) but the mechanism by which it interacts has not yet been identified. A potential class of binding partners are Rab GTPases and Rab3A is known to associate with SVs and is involved in SV trafficking. We performed experiments to determine whether Rab3A interacts with Myo5a and whether it is required for transport of neuronal vesicles. In vitro motility assays performed with axoplasm from the squid giant axon showed a requirement for a Rab GTPase in Myo5a-dependent vesicle transport. Furthermore, mouse recombinant Myo5a tail revealed that it associated with Rab3A in rat brain synaptosomal preparations in vitro and the association was confirmed by immunofluorescence imaging of primary neurons isolated from the frontal cortex of mouse brains. Synaptosomal Rab3A was retained on recombinant GST-tagged Myo5a tail affinity columns in a GTP-dependent manner. Finally, the direct interaction of Myo5a and Rab3A was determined by sedimentation velocity analytical ultracentrifugation using recombinant mouse Myo5a tail and human Rab3A. When both proteins were incubated in the presence of 1 mM GTP␥S, Myo5a tail and Rab3A formed a complex and a direct interaction was observed. Further analysis revealed that GTP-bound Rab3A interacts with both the monomeric and dimeric species of the Myo5a tail. However, the interaction between Myo5a tail and nucleotidefree Rab3A did not occur. Thus, our results show that Myo5a and Rab3A are direct binding partners and interact on SVs and that the Myo5a/Rab3A complex is involved in transport of neuronal vesicles.

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Section: Discussionsupporting

confidence: 80%

Myosin5a Tail Associates Directly with Rab3A-containing Compartments in Neurons

Wöllert

Patel

Lee

et al. 2011

Journal of Biological Chemistry

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“…Myosin-Va has a role in different aspects of the traffic of several vesicular carriers (Desnos et al, 2007;Eichler et al, 2006). It has been shown to be important in retaining these vesicular carriers (melanosomes, secretory granules) in the F-actin-rich cortex (Rudolf et al, 2003;Wu et al, 1998), and recently a role in fusion and exocytosis has also been reported via the interaction of myosin-Va with syntaxin-1A (Watanabe et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Myosin-Va restrains the trafficking of Na+/K+-ATPase-containing vesicles in alveolar epithelial cells

Lecuona

Минин

Trejo

et al. 2009

Journal of Cell Science

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Stimulation of Na+/K+-ATPase activity in alveolar epithelial cells by cAMP involves its recruitment from intracellular compartments to the plasma membrane. Here, we studied the role of the actin molecular motor myosin-V in this process. We provide evidence that, in alveolar epithelial cells, cAMP promotes Na+/K+-ATPase recruitment to the plasma membrane by increasing the average speed of Na+/K+-ATPase-containing vesicles moving to the cell periphery. We found that three isoforms of myosin-V are expressed in alveolar epithelial cells; however, only myosin-Va and Vc colocalized with the Na+/K+-ATPase in intracellular membrane fractions. Overexpression of dominant-negative myosin-Va or knockdown with specific shRNA increased the average speed and distance traveled by the Na+/K+-ATPase-containing vesicles, as well as the Na+/K+-ATPase activity and protein abundance at the plasma membrane to similar levels as those observed with cAMP stimulation. These data show that myosin-Va has a role in restraining Na+/K+-ATPase-containing vesicles within intracellular pools and that this restrain is released after stimulation by cAMP allowing the recruitment of the Na+/K+-ATPase to the plasma membrane and thus increased activity.

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“…MyoVa has been implicated in transport of secretory granules and melanosomes to the cell surfaces of neuroendocrine cells (6,22) and melanocytes, respectively (36). Through the use of two different dominant negative myosin Va (DNmyoVa) constructs lacking the actin-binding domain but con- HSV alters the conformation of myoVa as indicated by a substantial increase in immunostaining with a myoVa-specific polyclonal antibody starting at about 4 hpi with HSV-1 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Myosin Va Enhances Secretion of Herpes Simplex Virus 1 Virions and Cell Surface Expression of Viral Glycoproteins

Roberts

Baines

2010

J Virol

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The final step in the egress of herpes simplex virus (HSV) virions requires virion-laden vesicles to bypass cortical actin and fuse with the plasma membrane, releasing virions into the extracellular space. Little is known about the host or viral proteins involved. In the current study, we noted that the conformation of myosin Va (myoVa), a protein known to be involved in melanosome and secretory granule trafficking to the plasma membrane in melanocytes and neuroendocrine cells, respectively, was altered by 4 h after infection with HSV-1 such that an N-terminal epitope expected to be masked in its inactive state was rendered immunoreactive. Wild-type myoVa localized throughout the cytoplasm and to a limited extent in the nuclei of HSV-infected cells. Two different dominant negative myoVa molecules containing cargo-binding domains but lacking the lever arms and actin-binding domains colocalized with markers of the trans-Golgi network (TGN). Expression of dominant negative myoVa isoforms reduced secretion of HSV-1 infectivity into the medium by 50 to 75%, reduced surface expression of glycoproteins B, M, and D, and increased intracellular virus infectivity to levels consistent with increased retention of virions in the cytoplasm. These data suggest that myoVa is activated during HSV-1 infection to help transport virion-and glycoprotein-laden vesicles from the TGN, through the cortical actin, to the plasma membrane. We cannot exclude a role for myoVa in promoting fusion of these vesicles with the inner surface of the plasma membrane. These data also indicate that myoVa is involved in exocytosis in human epithelial cells as well as other cell types.Herpes simplex virus (HSV) virions, like those of all herpesviruses, comprise a lipid envelope surrounding a layer of proteins called the tegument that covers the surface of the proteinaceous DNA-containing capsid. After assembly in the nucleus, herpes simplex virus nucleocapsids bud through the inner nuclear membrane to obtain an initial virion envelope. In the most widely accepted model of virion egress, the envelopes of nascent virions residing in the perinuclear space then fuse with the outer nuclear membrane, releasing the de-enveloped capsid into the cytoplasm (25). The now cytosolic capsid then buds into a membranous organelle in the cytoplasm to obtain its final envelope. The site of secondary envelopment where the final budding event occurs is believed to contain markers of the trans-Golgi network (TGN) (28) and would be expected to contain the full complement of virion envelope and tegument proteins. Cellular budding machinery would also be expected to be involved, such as that required for multivesicular body formation (1, 4). Other models of virion egress propose that nucleocapsids can exit the nucleus through an expanded nuclear pore (33, 34), or that the original virion envelope derived from the inner nuclear membrane is retained throughout egress (13). In the latter scenario, enveloped virions are incorporated into a vesicle derived from the outer nuclear me...

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The role of myosin Va in secretory granule trafficking and exocytosis

Cited by 39 publications

References 42 publications

Myosin5a Tail Associates Directly with Rab3A-containing Compartments in Neurons

Myosin5a Tail Associates Directly with Rab3A-containing Compartments in Neurons

Myosin-Va restrains the trafficking of Na+/K+-ATPase-containing vesicles in alveolar epithelial cells

Myosin Va Enhances Secretion of Herpes Simplex Virus 1 Virions and Cell Surface Expression of Viral Glycoproteins

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