Myosin VI and Optineurin Are Required for Polarized EGFR Delivery and Directed Migration
نویسندگان
چکیده
The polarized trafficking of membrane proteins into the leading edge of the cell is an integral requirement for cell migration. Myosin VI and its interacting protein optineurin have previously been shown to operate in anterograde trafficking pathways, especially for the polarized delivery of cargo to the basolateral domain in epithelial cells. Here we show that in migratory cells ablation of myosin VI or optineurin inhibits the polarized delivery of the epidermal growth factor receptor (EGFR) into the leading edge and leads to profound defects in lamellipodia formation. Depletion of either myosin VI or optineurin, however, does not impair the overall ability of cells to migrate in a random migration assay, but it dramatically reduces directed migration towards a growth factor stimulus. In summary, we identified a specific role for myosin VI and optineurin in directionally persistent cell migration, which involves the polarized delivery of vesicles containing EGFR into the leading edge of the cell.
منابع مشابه
Myosin VI is required for sorting of AP-1B–dependent cargo to the basolateral domain in polarized MDCK cells
In polarized epithelial cells, newly synthesized membrane proteins are delivered on specific pathways to either the apical or basolateral domains, depending on the sorting motifs present in these proteins. Because myosin VI has been shown to facilitate secretory traffic in nonpolarized cells, we investigated its role in biosynthetic trafficking pathways in polarized MDCK cells. We observed that...
متن کاملMyosin VI and its binding partner optineurin are involved in secretory vesicle fusion at the plasma membrane
During constitutive secretion, proteins synthesized at the endoplasmic reticulum (ER) are transported to the Golgi complex for processing and then to the plasma membrane for incorporation or extracellular release. This study uses a unique live-cell constitutive secretion assay to establish roles for the molecular motor myosin VI and its binding partner optineurin in discrete stages of secretion...
متن کاملMultifunctional myosin VI has a multitude of cargoes.
I n humans, a vast array of cytoskeletal motor proteins (19 dyneins, 43 kinesins, and 39 myosins) (1) move along microtubule and actin filament tracks to generate an enormous range of cellular functions. The kinesin and dynein motor proteins drive long-distance transport along microtubules, whereas the myosins are responsible for short-range delivery along actin filaments (2). The myosin motor ...
متن کاملDefects in optineurin- and myosin VI-mediated cellular trafficking in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder primarily affecting motor neurons. Mutations in optineurin cause a small proportion of familial ALS cases, and wild-type (WT) optineurin is misfolded and forms inclusions in sporadic ALS patient motor neurons. However, it is unknown how optineurin mutation or misfolding leads to ALS. Optineurin acts an adaptor protein con...
متن کاملOptineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis
Myosin VI plays a role in the maintenance of Golgi morphology and in exocytosis. In a yeast 2-hybrid screen we identified optineurin as a binding partner for myosin VI at the Golgi complex and confirmed this interaction in a range of protein interaction studies. Both proteins colocalize at the Golgi complex and in vesicles at the plasma membrane. When optineurin is depleted from cells using RNA...
متن کامل