Phospholipid localization implies microglial morphology and function via Cdc42 in vitro.
Under a quiescent state, microglia exhibit a ramified shape, rather than the amoeboid-like morphology following injury or inflammation. The manipulation of microglial morphology in vitro has not been very successful, which has impeded the progress of microglial studies. We demonstrate that lysophosphatidylserine (LysoPS), a kind of lysophospholipids, rapidly and substantially alters the morphology of primary cultured microglia to an in vivo-like ramified shape in a receptor independent manner. This mechanism is mediated by Cdc42 activity. LysoPS is incorporated into the plasma membrane and converted to phosphatidylserine (PS) via the Lands' cycle. The accumulated PS on the membrane recruits Cdc42. Both Cdc42 and PS colocalize predominantly in primary and secondary processes, but not in peripheral branches or tips of microglia. Along with the morphological changes LysoPS suppresses inflammatory cytokine production and NF-kB activity. The present study provides a tool to manipulate a microglial phenotype from an amoeboid to a fully ramified in vitro, which certainly contributes to studies exploring microglial physiology and pathology.
Department of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of Medicine, Nagoya, 65 Tsurumai-cho, Showa-ku, Aichi, 466-8550, Japan.
Kyohei
K
Tokizane
Department of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of Medicine, Nagoya, 65 Tsurumai-cho, Showa-ku, Aichi, 466-8550, Japan.
Hiroyuki
H
Konishi
Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
Kumiko
K
Makide
Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
Hiroki
H
Kawana
Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, Nagoya, 65 Tsurumai-cho, Showa-ku, Aichi, 466-8550, Japan.
Shinichi
S
Nakamuta
Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, Nagoya, 65 Tsurumai-cho, Showa-ku, Aichi, 466-8550, Japan.
Kozo
K
Kaibuchi
Laboratory of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Tomohiko
T
Ohwada
Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
Junken
J
Aoki
Department of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of Medicine, Nagoya, 65 Tsurumai-cho, Showa-ku, Aichi, 466-8550, Japan.
Hiroshi
0000-0001-5963-046X
H
Kiyama
D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
C581598:Cdc42 protein, mouse; D008246:Lysophospholipids; D016328:NF-kappa B; C025059:lysophosphatidylserine; D020764:cdc42 GTP-Binding Protein; C032881:lysophosphatidic acid
NF-kB; lysophospholipid; phosphatidylserine; pro-inflammatory cytokines; ramified microglia