title: SYT14L, especially its C2 domain, is involved in regulating melanocyte differentiation.
abstract: BACKGROUND
  The formation of dendrites by melanocytes is highly analogous to that process in neural cells. We previously reported that a C2 domain-containing protein, copine-1, is involved in the extension of dendrites by neural cells. However, the effect of C2 domain-containing proteins in dendrite formation by melanocytes has not yet been elucidated.
  
  
  OBJECTIVE
  The aim of this study was to screen novel C2 domain-containing proteins related to dendrite outgrowth in melanocytes and to investigate their precise roles in melanocyte dendrite formation during differentiation.
  
  
  METHODS
  We transduced mouse melan-a melanocytes with a recombinant adenovirus expressing a C2 domain library. Dendrite elongation, melanin content, tyrosinase activity and Western blot analyses were conducted to elucidate the possible underlying mechanisms of action in melanocytes.
  
  
  RESULTS
  Sixteen sets of C2 domain-containing proteins were identified whose over-expression resulted in dendrite lengthening. Among those, we focused on the C2 domain of SYT14L (truncated mutant of SYT14L) in this study. Forced expression of full length SYT14L or the C2 domain of SYT14L induced a significant elongation of dendrite length accompanied by the induction of melanocyte differentiation-related markers, including melanin synthesis, tyrosinase catalytic activity and the expression of tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and TRP-2. In addition, over-expression of either the C2 domain or the full length form of SYT14L significantly increased the phosphorylation of ERK and CREB.
  
  
  CONCLUSIONS
  These results suggest that SYT14L, especially its C2 domain, may play an important role in regulating melanocyte differentiation through the modulation of ERK and (or) CREB signaling.
authors.affiliation: Department of Physiology, Institute of Health Sciences and Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Jinju 660-751, Republic of Korea.
authors.forename: Jae Cheal
authors.initials: JC
authors.lastname: Yoo
authors.forename: Tae yeon
authors.initials: Ty
authors.lastname: Lim
authors.forename: Jin Sung
authors.initials: JS
authors.lastname: Park
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.forename: Nammi
authors.initials: N
authors.lastname: Park
authors.forename: Seong-Geun
authors.initials: SG
authors.lastname: Hong
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Yoon
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002454:Cell Differentiation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003712:Dendrites / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D050857:Synaptotagmins / Q000502:physiology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C508557:SYT14P1 protein, human; D050857:Synaptotagmins; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: C2 domain; Dendrite; Melanocyte differentiation; SYT14L