Par-1 controls myosin-II activity through myosin phosphatase to regulate border cell migration.
BACKGROUND
Localized actomyosin contraction couples with actin polymerization and cell-matrix adhesion to regulate cell protrusions and retract trailing edges of migrating cells. Although many cells migrate in collective groups during tissue morphogenesis, mechanisms that coordinate actomyosin dynamics in collective cell migration are poorly understood. Migration of Drosophila border cells, a genetically tractable model for collective cell migration, requires nonmuscle myosin-II (Myo-II). How Myo-II specifically controls border cell migration and how Myo-II is itself regulated is largely unknown.


RESULTS
We show that Myo-II regulates two essential features of border cell migration: (1) initial detachment of the border cell cluster from the follicular epithelium and (2) the dynamics of cellular protrusions. We further demonstrate that the cell polarity protein Par-1 (MARK), a serine-threonine kinase, regulates the localization and activation of Myo-II in border cells. Par-1 binds to myosin phosphatase and phosphorylates it at a known inactivating site. Par-1 thus promotes phosphorylated myosin regulatory light chain, thereby increasing Myo-II activity. Furthermore, Par-1 localizes to and increases active Myo-II at the cluster rear to promote detachment; in the absence of Par-1, spatially distinct active Myo-II is lost.


CONCLUSIONS
We identify a critical new role for Par-1 kinase: spatiotemporal regulation of Myo-II activity within the border cell cluster through localized inhibition of myosin phosphatase. Polarity proteins such as Par-1, which intrinsically localize, can thus directly modulate the actomyosin dynamics required for border cell detachment and migration. Such a link between polarity proteins and cytoskeletal dynamics may also occur in other collective cell migrations.
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Pralay
P
Majumder
George
G
Aranjuez
Joseph
J
Amick
Jocelyn A
JA
McDonald
D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D010766:Phosphorylation
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D000205:Actomyosin; D038362:Glycogen Synthase Kinase 3; C472496:Par-1 protein, Drosophila; D043263:Myosin-Light-Chain Phosphatase; D024462:Myosin Type II