PMID- 32501289
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20230829
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 133
IP  - 13
DP  - 2020 Jul 8
TI  - Cofilin is required for polarization of tension in stress fiber networks during 
      migration.
LID - 10.1242/jcs.243873 [doi]
LID - jcs243873
AB  - Cell migration is associated with the establishment of defined leading and 
      trailing edges, which in turn requires polarization of contractile forces. While 
      the actomyosin stress fiber (SF) network plays a critical role in enforcing this 
      polarity, precisely how this asymmetry is established remains unclear. Here, we 
      provide evidence for a model in which the actin-severing protein cofilin 
      (specifically cofilin-1) participates in symmetry breakage by removing 
      low-tension actomyosin filaments during transverse arc assembly. Cofilin 
      knockdown (KD) produces a non-polarized SF architecture that cannot be rescued 
      with chemokines or asymmetric matrix patterns. Whereas cofilin KD increases 
      whole-cell prestress, it decreases prestress within single SFs, implying an 
      accumulation of low-tension SFs. This notion is supported by time-lapse imaging, 
      which reveals weakly contractile and incompletely fused transverse arcs. Confocal 
      and super-resolution imaging further associate this failed fusion with the 
      presence of crosslinker-rich, tropomyosin-devoid nodes at the junctions of 
      multiple transverse arc fragments and dorsal SFs. These results support a model 
      in which cofilin facilitates the formation of high-tension transverse arcs, 
      thereby promoting mechanical asymmetry.
CI  - (c) 2020. Published by The Company of Biologists Ltd.
FAU - Lee, Stacey
AU  - Lee S
AUID- ORCID: 0000-0001-5645-8449
AD  - UC Berkeley-UCSF Graduate Program in Bioengineering, USA.
AD  - UC Berkeley Department of Bioengineering, UC Berkeley, CA, USA.
FAU - Kumar, Sanjay
AU  - Kumar S
AUID- ORCID: 0000-0002-9996-4883
AD  - UC Berkeley-UCSF Graduate Program in Bioengineering, USA skumar@berkeley.edu.
AD  - UC Berkeley Department of Bioengineering, UC Berkeley, CA, USA.
AD  - UC Berkeley Department of Chemical and Biomolecular Engineering, 274A Stanley 
      Hall #1762, UC Berkeley, Berkeley, CA 94720-1762, UC Berkeley, CA, USA.
LA  - eng
GR  - F31 GM119329/GM/NIGMS NIH HHS/United States
GR  - R01 GM122375/GM/NIGMS NIH HHS/United States
GR  - R21 EB016359/EB/NIBIB NIH HHS/United States
GR  - S10 OD018136/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200708
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Actin Depolymerizing Factors)
RN  - 0 (Actins)
RN  - 0 (Cofilin 1)
RN  - 9013-26-7 (Actomyosin)
SB  - IM
MH  - Actin Cytoskeleton
MH  - *Actin Depolymerizing Factors
MH  - Actins/genetics
MH  - Actomyosin
MH  - Cofilin 1/genetics
MH  - Cytoskeleton
MH  - *Stress Fibers
PMC - PMC7358140
OTO - NOTNLM
OT  - Cell mechanics
OT  - Cofilin
OT  - Front-back polarity
OT  - Stress fiber
OT  - Tension
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2020/06/06 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/07/08
CRDT- 2020/06/06 06:00
PHST- 2020/01/14 00:00 [received]
PHST- 2020/05/11 00:00 [accepted]
PHST- 2020/06/06 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/06 06:00 [entrez]
PHST- 2021/07/08 00:00 [pmc-release]
AID - jcs.243873 [pii]
AID - JCS243873 [pii]
AID - 10.1242/jcs.243873 [doi]
PST - epublish
SO  - J Cell Sci. 2020 Jul 8;133(13):jcs243873. doi: 10.1242/jcs.243873.