TY - JOUR
T1 - Keratocyte fragments and cells utilize competing pathways to move in opposite directions in an electric field
AU - Sun, Yaohui
AU - Do, Hao
AU - Gao, Jing
AU - Zhao, Ren
AU - Zhao, Min
AU - Mogilner, Alex
N1 - Funding Information:
We are grateful to Greg Allen, Orion Weiner, and Roy Wollman for fruitful discussions, useful suggestions, and critical reading of this manuscript. We thank Noa Ofer and Kinneret Keren for sharing endoplasmic reticulum images. This work was supported by National Institutes of Health grants GM068952 to A.M. and 1R01EY019101 to M.Z., as well as by California Institute of Regenerative Medicine Research grant RB1-01417 and National Science Foundation Grant MCB-0951199 to M.Z and P. Devreotes, whose support we gratefully acknowledge.
PY - 2013/4/8
Y1 - 2013/4/8
N2 - Sensing of an electric field (EF) by cells - galvanotaxis - is important in wound healing [1], development [2], cell division, nerve growth, and angiogenesis [3]. Different cell types migrate in opposite directions in EFs [4], and the same cell can switch the directionality depending on conditions [5]. A tug-of-war mechanism between multiple signaling pathways [6] can direct Dictyostelium cells to either cathode or anode. Mechanics of motility is simplest in fish keratocytes, so we turned to keratocytes to investigate their migration in EFs. Keratocytes sense electric fields and migrate to the cathode [7, 8]. Keratocyte fragments [9, 10] are the simplest motile units. Cell fragments from leukocytes are able to respond to chemotactic signals [11], but whether cell fragments are galvanotactic was unknown. We found that keratocyte fragments are the smallest motile electric field-sensing unit: they migrate to the anode, in the opposite direction of whole cells. Myosin II was essential for the direction sensing of fragments but not for parental cells, while PI3 kinase was essential for the direction sensing of whole cells but not for fragments. Thus, two signal transduction pathways, one depending on PI3K, another on myosin, compete to orient motile cells in the electric field. Galvanotaxis is not due to EF force and does not depend on cell or fragment size. We propose a "compass" model according to which protrusive and contractile actomyosin networks self-polarize to the front and rear of the motile cell, respectively, and the electric signal orients both networks toward cathode with different strengths.
AB - Sensing of an electric field (EF) by cells - galvanotaxis - is important in wound healing [1], development [2], cell division, nerve growth, and angiogenesis [3]. Different cell types migrate in opposite directions in EFs [4], and the same cell can switch the directionality depending on conditions [5]. A tug-of-war mechanism between multiple signaling pathways [6] can direct Dictyostelium cells to either cathode or anode. Mechanics of motility is simplest in fish keratocytes, so we turned to keratocytes to investigate their migration in EFs. Keratocytes sense electric fields and migrate to the cathode [7, 8]. Keratocyte fragments [9, 10] are the simplest motile units. Cell fragments from leukocytes are able to respond to chemotactic signals [11], but whether cell fragments are galvanotactic was unknown. We found that keratocyte fragments are the smallest motile electric field-sensing unit: they migrate to the anode, in the opposite direction of whole cells. Myosin II was essential for the direction sensing of fragments but not for parental cells, while PI3 kinase was essential for the direction sensing of whole cells but not for fragments. Thus, two signal transduction pathways, one depending on PI3K, another on myosin, compete to orient motile cells in the electric field. Galvanotaxis is not due to EF force and does not depend on cell or fragment size. We propose a "compass" model according to which protrusive and contractile actomyosin networks self-polarize to the front and rear of the motile cell, respectively, and the electric signal orients both networks toward cathode with different strengths.
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U2 - 10.1016/j.cub.2013.02.026
DO - 10.1016/j.cub.2013.02.026
M3 - Article
C2 - 23541726
AN - SCOPUS:84876156325
SN - 0960-9822
VL - 23
SP - 569
EP - 574
JO - Current Biology
JF - Current Biology
IS - 7
ER -