Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation.
Angiomotin (Amot), the founding member of the Motin family, is involved in angiogenesis by regulating endothelial cell motility, and is required for visceral endoderm movement in mice. However, little is known about biological functions of the other two members of the Motin family, Angiomotin-like1 (Amotl1) and Angiomotin-like2 (Amotl2). Here, we have identified zebrafish amotl2 as an Fgf-responsive gene. Zebrafish amotl2 is expressed maternally and in restricted cell types zygotically. Knockdown of amotl2 expression delays epiboly and impairs convergence and extension movement, and amotl2-deficient cells in mosaic embryos fail to migrate properly. This coincides with loss of membrane protrusions and disorder of F-actin. Amotl2 partially co-localizes with RhoB-or EEA1-positive endosomes and the non-receptor tyrosine kinase c-Src. We further demonstrate that Amotl2 interacts preferentially with and facilitates outward translocation of the phosphorylated c-Src, which may in turn regulate the membrane architecture. These data provide the first evidence that amotl2 is essential for cell movements in vertebrate embryos.
Huang
Huizhe
H
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Lu
Fu-I
FI
Jia
Shunji
S
Meng
Shu
S
Cao
Ying
Y
Wang
Yeqi
Y
Ma
Weiping
W
Yin
Kun
K
Wen
Zilong
Z
Peng
Jingrong
J
Thisse
Christine
C
Thisse
Bernard
B
Meng
Anming
A
D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000502:physiology; D000595:Amino Acid Sequence; D000091082:Angiomotins; D000818:Animals; D019521:Body Patterning; D002465:Cell Movement / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D011992:Endosomes / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D021381:Protein Transport; D011554:Pseudopodia / Q000502:physiology; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*; D020743:rhoB GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D000199:Actins; D000091082:Angiomotins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; D029961:Zebrafish Proteins; C519597:amotl2a protein, zebrafish; D005346:Fibroblast Growth Factors; D019061:src-Family Kinases; D020743:rhoB GTP-Binding Protein