Lipid domain-dependent regulation of single-cell wound repair.
After damage, cells reseal their plasma membrane and repair the underlying cortical cytoskeleton. Although many different proteins have been implicated in cell repair, the potential role of specific lipids has not been explored. Here we report that cell damage elicits rapid formation of spatially organized lipid domains around the damage site, with different lipids concentrated in different domains as a result of both de novo synthesis and transport. One of these lipids-diacylglycerol (DAG)-rapidly accumulates in a broad domain that overlaps the zones of active Rho and Cdc42, GTPases that regulate repair of the cortical cytoskeleton. Formation of the DAG domain is required for Cdc42 and Rho activation and healing. Two DAG targets, protein kinase C (PKC) β and η, are recruited to cell wounds and play mutually antagonistic roles in the healing process: PKCβ participates in Rho and Cdc42 activation, whereas PKCη inhibits Rho and Cdc42 activation. The results reveal an unexpected diversity in subcellular lipid domains and the importance of such domains for a basic cellular process.
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706Department of Zoology, University of Wisconsin-Madison, Madison, WI 53706.
Emily M
EM
Vaughan
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706.
Jae-Sung
JS
You
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706Department of Zoology, University of Wisconsin-Madison, Madison, WI 53706.
Hoi-Ying
HY
Elsie Yu
Department of Zoology, University of Wisconsin-Madison, Madison, WI 53706.
Amber
A
Lasek
Institut des Neurosciences Cellulaires et Integratives, Centre National de la Recherche Scientifique UPR 3212, and Université de Strasbourg, 67400 Strasbourg, France.
Nicolas
N
Vitale
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706.
Troy A
TA
Hornberger
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706Department of Zoology, University of Wisconsin-Madison, Madison, WI 53706Laboratory of Cell and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706 wmbement@wisc.edu.
William M
WM
Bement
D000818:Animals; D021961:Cell Membrane Structures / Q000502:physiology*; D019852:Diacylglycerol Kinase / Q000378:metabolism; D004075:Diglycerides / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D021381:Protein Transport; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism; D059010:Single-Cell Analysis; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis
D004075:Diglycerides; D010713:Phosphatidylcholines; D064067:Rho Guanine Nucleotide Exchange Factors; D029867:Xenopus Proteins; D019852:Diacylglycerol Kinase; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase; D010738:Type C Phospholipases; D010739:Phospholipase D; C559910:Cdc42 protein, Xenopus; D020559:Monomeric GTP-Binding Proteins