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dictyNews Volume 39 Number 29
dictyNews
Electronic Edition
Volume 39, number 29
October 11, 2013
Please submit abstracts of your papers as soon as they have been
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or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.
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Abstracts
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Luo T, Mohan K, Iglesias PA, Robinson DN.
Molecular mechanisms of cellular mechanosensing
Nat. Mater. 2013, in press.
Mechanical forces direct a host of cellular and tissue processes.
Although much emphasis has been placed on cell-adhesion
complexes as force sensors, the forces must nevertheless be
transmitted through the cortical cytoskeleton. Yet how the actin
cortex senses and transmits forces and how cytoskeletal proteins
interact in response to the forces is poorly understood. Here, by
combining molecular and mechanical experimental perturbations
with theoretical multiscale modelling, we decipher cortical
mechanosensing from molecular to cellular scales. We show that
forces are shared between myosin II and different actin crosslinkers,
with myosin having potentiating or inhibitory effects on certain
crosslinkers. Different types of cell deformation elicit distinct
responses, with myosin and alpha-actinin responding to dilation,
and filamin mainly reacting to shear. Our observations show that
the accumulation kinetics of each protein may be explained by its
molecular mechanisms, and that protein accumulation and the
cellÕs viscoelastic state can explain cell contraction against
mechanical load.
Submitted by Douglas Robinson [dnr@jhmi.edu]
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Phosphorylation of chemoattractant receptors regulates
chemotaxis, actin reorganization and signal relay
Joseph A. Brzostowski1,*, Satoshi Sawai2, Orr Rozov1,à,
Xin-hua Liao3,¤, Daisuke Imoto4, Carole A. Parent5 and
Alan R. Kimmel3,*
1Laboratory of Immunogenetics Imaging Facility, NIAID/NIH,
Rockville, MD 20852, USA
2Graduate School of Arts and Sciences, University of Tokyo and
PRESTO, JST, Tokyo 153-8902, Japan
3Laboratory of Cellular and Developmental Biology, NIDDK/NIH,
Bethesda, MD 20892, USA
4Graduate School of Arts and Sciences, University of Tokyo,
Tokyo 153-8902, Japan
5Laboratory of Cellular and Molecular Biology, NCI/NIH, Bethesda,
MD 20892, USA
*Authors for correspondence (jb363a@nih.gov; alank@helix.nih.gov)
J Cell Sci126, 4614-4626
Migratory cells, including mammalian leukocytes and Dictyostelium,
use G-protein-coupled receptor (GPCR) signaling to regulate
MAPK/ERK, PI3K, TORC2/AKT, adenylyl cyclase and actin
polymerization, which collectively direct chemotaxis. Upon ligand
binding, mammalian GPCRs are phosphorylated at cytoplasmic
residues, uncoupling G-protein pathways, but activating other
pathways. However, connections between GPCR phosphorylation
and chemotaxis are unclear. In developing Dictyostelium, secreted
cAMP serves as a chemoattractant, with extracellular cAMP
propagated as oscillating waves to ensure directional migratory
signals. cAMP oscillations derive from transient excitatory responses
of adenylyl cyclase, which then rapidly adapts. We have studied
chemotactic signaling in Dictyostelium that express non-
phosphorylatable cAMP receptors and show through chemotaxis
modeling, single-cell FRET imaging, pure and chimeric population
wavelet quantification, biochemical analyses and TIRF microscopy,
that receptor phosphorylation is required to regulate adenylyl
cyclase adaptation, long-range oscillatory cAMP wave production
and cytoskeletal actin response. Phosphorylation defects thus
promote hyperactive actin polymerization at the cell periphery,
misdirected pseudopodia and the loss of directional chemotaxis.
Our data indicate that chemoattractant receptor phosphorylation is
required to co-regulate essential pathways for migratory cell
polarization and chemotaxis. Our results significantly extend the
understanding of the function of GPCR phosphorylation, providing
strong evidence that this evolutionarily conserved mechanism is
required in a signal attenuation pathway that is necessary to
maintain persistent directional movement of Dictyostelium,
neutrophils and other migratory cells.
Submitted by Joe Brzostowski [brzostowskij@niaid.nih.gov]
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[End dictyNews, volume 39, number 29]
