Lysophosphatidylcholine mediates melanocyte dendricity through PKCzeta activation.
Melanocytes photoprotect the skin through transfer of melanin-containing melanosomes to keratinocytes. Factors that increase melanocyte dendricity increase melanosome transfer, and are important for prevention of skin cancer. Secretory phospholipase-A2 type X (sPLA2-X) is released by epidermal keratinocytes and we have shown that lysophosphatidylcholine (LPC), the main lysophospholipid released in response to sPLA2-X activity, stimulates melanocyte dendricity. LPC activates protein kinase C (PKC) and increases cAMP in other cells. Treatment of melanocytes with sPLA2-X or LPC induced phosphorylation of the zeta isoform of PKC, and inhibition of protein kinase C zeta (PKCzeta) activity abrogated LPC-dependent dendricity. We have shown previously that the guanosine triphosphate-binding proteins Rac and Rho link hormone signaling and dendricity in melanocytes. Treatment of melanocytes with LPC induced rapid activation of Rac that peaked at 30 minutes; Rho was also activated, but peaked earlier and declined faster. Through the use of constitutively active mutants of Rac, we show that PKCzeta activation is downstream of Rac. We conclude that the primary signaling pathway for LPC-dependent dendrite formation in human melanocytes involves the activation of PKCzeta and that PKCzeta phosphorylation is Rac dependent. Downstream mediators of LPC-dependent dendricity include Rac and Rho.
Scott
Glynis A
GA
Department of Dermatology, University of Rochester School of Medicine, Rochester, New York 14642, USA. glynis_scott@urmc.rochester.edu
Arioka
Manubu
M
Jacobs
Stacey E
SE
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology*; D004789:Enzyme Activation; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism*; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010766:Phosphorylation; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010741:Phospholipases A; D054467:Phospholipases A2; D020033:Protein Isoforms; D011493:Protein Kinase C; D011994:Recombinant Proteins; D020744:rac GTP-Binding Proteins; D000099221:Protein Kinase C zeta