Caveolin-1α and -1β perform nonredundant roles in early vertebrate development

被引:43
作者
Fang, Ping-Ke
Solomon, Keith R.
Zhuang, Liyan
Qi, Maosong
McKee, Mary
Freeman, Michael R.
Yelick, Pamela C.
机构
[1] Harvard Univ, Sch Med, Urol Dis Res Ctr, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Orthopaed Surg, Childrens Hosp Boston, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, Boston, MA 02114 USA
[4] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA
关键词
D O I
10.2353/ajpath.2006.060562
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Caveolins are integral membrane proteins that localize predominantly to lipid rafts, where they oligomerize to form flask-shaped organelles termed caveolae and play important roles in membrane trafficking, signal transduction, and other cellular processes. To investigate potential roles for caveolin-1 (cav-1) in development, cav-1 alpha and -1 beta cDNAs were functionally characterized in the zebrafish. Cav-1 alpha and -1 beta mRNAs exhibited overlapping but distinct expression patterns throughout embryogenesis. Targeted depletion of either Cav-1 isoform, using antisense morpholino, oligomers, resulted in a substantial loss of caveolae and dramatic neural, eye, and somite defects by 12 hours after fertilization, the time at which mRNA levels of both isoforms substantially increased in wildtype animals. Morphant phenotypes were rescued by injection of homotypic (cav-1 alpha/cav-1 beta) but not heterotypic (cav-1 alpha/cav-1 beta) zebrafish and human cav-1 cRNAs, revealing nonredundant and evolutionarily conserved functions for the individual Cav-1 alpha isoforms. Mutation of a known Cav-1 phosphorylation site unique to Cav-1 alpha (Y14 -> F) resulted in a failure to rescue the cav-1 a morphant phenotype, verifying an essential role for Cav-1 beta specifically and implicating this residue in early developmental functions. Cav-1 alpha and -1 beta morphants also exhibited disruption in the actin cytoskeleton. These results support important and previously unanticipated roles for the Caveolin-1 isoforms in vertebrate organogenesis.
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页码:2209 / 2222
页数:14
相关论文
共 69 条
[1]  
[Anonymous], 1995, ZEBRAFISH BOOK
[2]   LOCALIZATION OF THE PHALLOIDIN AND NUCLEOTIDE-BINDING SITES ON ACTIN [J].
BARDEN, JA ;
MIKI, M ;
HAMBLY, BD ;
DOSREMEDIOS, CG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1987, 162 (03) :583-588
[3]   Regulation of integrin growth factor interactions in oligodendrocytes by lipid raft microdomains [J].
Baron, W ;
Decker, L ;
Colognato, H ;
ffrench-Constant, C .
CURRENT BIOLOGY, 2003, 13 (02) :151-155
[4]  
Becker KA, 1999, J CELL SCI, V112, P97
[5]   Actin-dependent pigment granule transport in retinal pigment epithelial cells [J].
Burnside, B ;
KingSmith, C .
BIOLOGICAL BULLETIN, 1997, 192 (01) :181-182
[6]   Ovine caveolin-1:: cDNA cloning, E. coli expression, and association with endothelial nitric oxide synthase [J].
Chen, DB ;
Zangl, AL ;
Zhao, Q ;
Markley, JL ;
Zheng, J ;
Bird, IM ;
Magness, R .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2001, 175 (1-2) :41-56
[7]   Integrins regulate Rac targeting by internalization of membrane domains [J].
del Pozo, MA ;
Alderson, NB ;
Kiosses, WB ;
Chiang, HH ;
Anderson, RGW ;
Schwartz, MA .
SCIENCE, 2004, 303 (5659) :839-842
[8]   Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice [J].
Drab, M ;
Verkade, P ;
Elger, M ;
Kasper, M ;
Lohn, M ;
Lauterbach, B ;
Menne, J ;
Lindschau, C ;
Mende, F ;
Luft, FC ;
Schedl, A ;
Haller, H ;
Kurzchalia, TV .
SCIENCE, 2001, 293 (5539) :2449-2452
[9]   The vesiculo-vacuolar organelle (VVO): A new endothelial cell permeability organelle [J].
Dvorak, AM ;
Feng, D .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2001, 49 (04) :419-431
[10]   PROBING THE PHALLOIDIN BINDING-SITE OF ACTIN [J].
FAULSTICH, H ;
ZOBELEY, S ;
HEINTZ, D ;
DREWES, G .
FEBS LETTERS, 1993, 318 (03) :218-222