CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells.
The alternative SDF-1 (stromal cell derived factor-1) receptor, CXCR7, has been suggested to act as either a scavenger of extracellular SDF-1 or a modulator of the primary SDF-1 receptor, CXCR4. CXCR7, however, also directly affects the function of various tumor-cell types. Here, we demonstrate that CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells. Cultured cortical astrocytes and peripheral nerve Schwann cells exhibit comparable total and cell-surface levels of expression of both SDF-1 receptors. Stimulation of astrocytes with SDF-1 resulted in the temporary activation of Erk1/2, Akt and PKCzeta/lambda, but not p38 and PKCalpha/beta. Schwann cells showed SDF-1-induced activation of Erk1/2, Akt and p38, but not PKCalpha/beta and PKCzeta/lambda. The respective signalling pattern remained fully inducible in astrocytes from CXCR4-deficient mice, but was abrogated following depletion of astrocytic CXCR7 by RNAi. In Schwann cells, RNAi-mediated depletion of either CXCR4 or CXCR7 silenced SDF-1 signalling. The findings of the astrocytic receptor-depletion experiments were reproduced by CXCR7 antagonist CCX754, but not by CXCR4 antagonist AMD3100, both of which abolished astrocytic SDF-1 signalling. Further underlining the functional importance of CXCR7 signalling in glial cells, we show that the mitogenic effects of SDF-1 on both glial cell types are impaired upon depleting CXCR7.
Odemis
Veysel
V
Institute of Anatomy, University of Leipzig, Medical Faculty, 04103 Leipzig, Germany.
Boosmann
Karina
K
Heinen
André
A
Küry
Patrick
P
Engele
Jürgen
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001596:Benzylamines; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054022:Cerebrum; D054377:Chemokine CXCL12 / Q000378:metabolism*; D000080027:Cyclams; D004622:Embryo, Mammalian; D006571:Heterocyclic Compounds / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
C501898:Ackr3 protein, rat; D001596:Benzylamines; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D034741:RNA, Small Interfering; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; C088327:plerixafor