Lysophosphatidic acid influences the morphology and motility of young, postmitotic cortical neurons.
Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that produces process retraction and cell rounding through its cognate receptors in neuroblastoma cell lines. Although the expression profile of LPA receptors in developing brains suggests a role for LPA in central nervous system (CNS) development, how LPA influences the morphology of postmitotic CNS neurons remains to be determined. Here we have investigated the effects of exogenous LPA on the morphology of young, postmitotic neurons in primary culture. When treated with LPA, these neurons responded by not only retracting processes but also producing retraction fiber "caps" characterized by fine actin filaments emanating from a dense core. Retraction fiber caps gradually vanished due to the outward spread of regrowing membranes along the fibers, suggesting a role for caps as scaffolds for regrowth of retracted processes. Furthermore, LPA also affects neuronal migration in vitro and in vivo. Taken together, these results implicate LPA as an extracellular lipid signal affecting process outgrowth and migration of early postmitotic neurons during development.
Fukushima
Nobuyuki
N
Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636, USA. nfuku@med.hokudai.ac.jp
Weiner
Joshua A
JA
Kaushal
Dhruv
D
Contos
James J A
JJ
Rehen
Stevens K
SK
Kingsbury
Marcy A
MA
Kim
Kyung Yong
KY
Chun
Jerold
J
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008246:Lysophospholipids / Q000172:deficiency* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011108:Polymers / Q000378:metabolism; D011247:Pregnancy; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
D008246:Lysophospholipids; D008869:Microtubule-Associated Proteins; D011108:Polymers; D012333:RNA, Messenger; D014404:Tubulin; D015638:Cytochalasin D