Stromal cell-derived factor 1-mediated CXCR4 signaling in rat and human cortical neural progenitor cells.
Stromal cell-derived factor 1 (SDF-1) and the chemokine receptor CXCR4 are highly expressed in the nervous system. Knockout studies have suggested that both SDF-1 and CXCR4 play essential roles in cerebellar, hippocampal, and neocortical neural cell migration during embryogenesis. To extend these observations, CXCR4 signaling events in rat and human neural progenitor cells (NPCs) were examined. Our results show that CXCR4 is expressed in abundance on rat and human NPCs. Moreover, SDF-1alpha induced increased NPCs levels of inositol 1,4,5-triphosphate, extracellular signal-regulated kinases 1/2, Akt, c-Jun N-terminal kinase, and intracellular calcium whereas it diminished cyclic adenosine monophosphate. Finally, SDF-1alpha can induce human NPC chemotaxis in vitro, suggesting that CXCR4 plays a functional role in NPC migration. Both T140, a CXCR4 antagonist, and pertussis toxin (PTX), an inactivator of G protein-coupled receptors, abrogated these events. Ultimately, this study suggested that SDF-1alpha can influence NPC function through CXCR4 and that CXCR4 is functional on NPC.
Peng
Hui
H
Laboratory of Neurotoxicology, the Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha 68198-5215, USA.
Huang
Yunlong
Y
Rose
Jeremy
J
Erichsen
David
D
Herek
Shelley
S
Fujii
Nobutaka
N
Tamamura
Hirokazu
H
Zheng
Jialin
J
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology; D002469:Cell Separation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D007293:Inosine Triphosphate / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D019718:Receptors, CXCR4 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D019718:Receptors, CXCR4; D007293:Inosine Triphosphate; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium