Myosin VI in PC12 cells plays important roles in cell migration and proliferation but not in catecholamine secretion

Abstract

Myosin VI (MVI) is the only known myosin walking towards minus end of actin filaments and is believed to play distinct role(s) than other myosins. We addressed a role of this unique motor in secretory PC12 cells, derived from rat adrenal medulla pheochromocytoma using cell lines with reduced MVI synthesis (produced by means of siRNA). Decrease of MVI expression caused severe changes in cell size and morphology, and profound defects in actin cytoskeleton organization and Golgi structure. Also, significant inhibition of cell migration as well as cell proliferation was observed. Flow cytometric analysis revealed that MVI-deficient cells were arrested in G0/G1 phase of the cell cycle but did not undergo increased senescence as compared with control cells. Also, neither polyploidy nor aneuploidy were detected. Surprisingly, no significant effect on noradrenaline secretion was observed. These data indicate that in PC12 cells MVI is involved in cell migration and proliferation but is not crucial for stimulation-dependent catecholamine release.

Myosin VI small insert isoform maintains exocytosis by tethering secretory granules to the cortical actin

“…Although myosin VI has recently been shown to be important for synaptic function in the Drosophila melanogaster neuromuscular junction (Kisiel et al, 2011), its precise role in neurosecretory cells remains to be elucidated, with its involvement in regulated secretion in these cells recently being questioned (Majewski et al, 2011). Here, we reveal a novel role for the myosin VI SI in tethering SGs to F-actin in response to stimulation.…”

Myosin VI Localization and Expression in Striated Muscle Pathology

“…The C‐terminal part of the tail forms a globular domain, which is essential for cargo binding through its interaction with binding partners (Sweeney and Houdusse, ; Chibalina et al, ; Karolczak et al, ; Tumbarello et al, ). The data gathered so far indicate that MVI acting as molecular motor and/or an anchor is engaged in endocytosis and intracellular transport of vesicles and organelles, cell migration, maintenance of the Golgi apparatus, actin cytoskeleton organization, autophagy and possibly in gene transcription (Vreugde et al, ; Sweeney and Houdusse, ; Chibalina et al, ; Majewski et al, ; Tumbarello et al, ).…”

Myosin VI small insert isoform maintains exocytosis by tethering secretory granules to the cortical actin

“…Myosin VI SI thus recruits SGs to the cortical actin network, potentially via c-Src phosphorylation, thereby maintaining an active pool of SGs near the plasma membrane. Although myosin VI has recently been shown to be important for synaptic function in the Drosophila melanogaster neuromuscular junction (Kisiel et al, 2011), its precise role in neurosecretory cells remains to be elucidated, with its involvement in regulated secretion in these cells recently being questioned (Majewski et al, 2011). Here, we reveal a novel role for the myosin VI SI in tethering SGs to F-actin in response to stimulation.…”

“…Myosin VI was of interest as it had previously been described to have an anchoring function that allows the attachment of membrane compartments to the actin cytoskeleton (Self et al, 1999;Buss and Kendrick-Jones, 2008). Although it was recently found to colocalize with an SG marker in PC12 cells, its role in regulated secretion remains a matter of debate (Majewski et al, 2011). Here, we provide the first demonstration that myosin VI interacts with SGs in a Ca 2+ -dependent manner and drives the tethering and retention of SGs to F-actin in the cortical actin network.…”