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Cell Migration

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Migration is a complex cycle requiring careful coordination of many cytoskeleton ... Isoforms exhibit unique phosphorylation events (Murakami et al., Biochemistry. ... – PowerPoint PPT presentation

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Title: Cell Migration


1
Cell Migration
  • Cell migration is critical for many processes
  • embryonic development
  • wound healing
  • tumor cell metastasis
  • Migration is a complex cycle requiring careful
    coordination of many cytoskeleton proteins
  • One important protein is myosin II

Sandquist, J.C. 2006
2
Myosin II
bipolar myosin filament
F-actin
  • Non-muscle myosin II is an ubiquitous motor
    protein that is able to bind and contract actin
    filaments
  • Invertebrates such as Dictyostelium, Drosophila
    and yeast harbor only one gene that encodes
    myosin II heavy chain
  • All vertebrates examined express at least two
    myosin II heavy chain isoforms (denoted IIA and
    IIB)

Sandquist, J.C. 2006
3
Myosin II
Direction of contraction
bipolar myosin filament
ATP
F-actin
ADP
  • Non-muscle myosin II is an ubiquitous motor
    protein that is able to bind and contract actin
    filaments
  • Invertebrates such as Dictyostelium, Drosophila
    and yeast harbor only one gene that encodes
    myosin II heavy chain
  • All vertebrates examined express at least two
    myosin II heavy chain isoforms (denoted IIA and
    IIB)

Sandquist, J.C. 2006
4
Myosin II Isoforms May Perform Distinct Cellular
Functions
  • Myosin IIA and IIB
  • Display different assembly and enzymatic
    properties in vitro (Kelley et al., J. Cell Biol.
    1996)
  • Exhibit differences in subcellular localization
    in motile cells (Kolega J., J. Cell Sci. 1998
    Maupin et al. J. Cell Sci. 1994 Rochlin et al.,
    J. Cell Sci. 1995))
  • Isoforms exhibit unique phosphorylation events
    (Murakami et al., Biochemistry. 1998
    Straussman et al., J. Cell Sci. 2001)
  • Null mice exhibit different phenotypes
    (Tullio et al., PNAS. 1997
    Conti et al., J. Biol Chem. 2004)

Do myosin IIA and IIB perform different functions
in cell migration?
5
Rho Kinase (ROCK) Regulates Myosin II Activity
Rho-GDP
Rho-GTP
Y-27632
Regulatory Light Chain (RLC)
ROCK
Myosin II Activation
RLC
MLCP
  • Phosphorylation on RLC increases myosin II
    activity
  • ROCK directly phosphorylates RLC and inhibits
    myosin light chain phosphatase (MLCP)
  • Y-27632 is a small molecule inhibitor of ROCK

Sandquist, J.C. 2006
6
Summary
  • IIA-depleted cells exhibit
  • migration rate
  • spreading/protrusion
  • focal adhesions
  • IIB-depleted cells exhibit
  • migration rate
  • spreading/protrusions
  • altered focal adhesions
  • How do IIA and IIB perform distinct functions?

Sandquist, J.C. 2006
7
Conclusions
  • IIA and IIB perform distinct functions during
    wound migration
  • IIA positively regulates adhesion and prohibits
    protrusive activity
  • IIB is required for proper cell
    spreading/protrusion
  • ROCK preferentially regulates IIA activity via
    regulation of IIA-RLC phosphorylation

Sandquist, J.C. 2006
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