The role of C. elegans Ena/VASP homolog UNC-34 in neuronal polarity and motility.
Ena/VASP proteins mediate the effects of guidance cues on the actin cytoskeleton. The single C. elegans homolog of the Ena/VASP family of proteins, UNC-34, is required for the migrations of cells and growth cones. Here we show that unc-34 mutant alleles also interact genetically with Wnt mutants to reveal a role for unc-34 in the establishment of neuronal polarity along the C. elegans anterior-posterior axis. Our mutant analysis shows that eliminating UNC-34 function results in neuronal migration and polarity phenotypes that are enhanced at higher temperatures, revealing a heat-sensitive process that is normally masked by the presence of UNC-34. Finally, we show that the UNC-34 protein is expressed broadly and accumulates in axons and at the apical junctions of epithelial cells. While most mutants lacked detectable UNC-34, three unc-34 mutants that contained missense mutations in the EVH1 domain produced full-length UNC-34 that failed to localize to apical junctions and axons, supporting the role for the EVH1 domain in localizing Ena/VASP family members.
Fleming
Tinya
T
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Chien
Shih-Chieh
SC
Vanderzalm
Pamela J
PJ
Dell
Megan
M
Gavin
Megan K
MK
Forrester
Wayne C
WC
Garriga
Gian
G
D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002465:Cell Movement; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006358:Hot Temperature; D008954:Models, Biological; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D034622:RNA Interference
D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C511070:unc-34 protein, C elegans
Curr Biol. 2006 May 9;16(9):845-53
16563765
Nat Neurosci. 2002 Nov;5(11):1147-54
12379860
Development. 1994 May;120(5):1035-47
8026318
EMBO J. 1995 Apr 3;14(7):1314-21
7729410
Dev Biol. 1983 Nov;100(1):64-119
6684600
Dev Cell. 2006 Mar;10(3):379-90
16516840
Philos Trans R Soc Lond B Biol Sci. 1986 Nov 12;314(1165):1-340
22462104
Genes Dev. 1996 Jun 1;10(11):1395-410
8647436
Cell. 1997 Aug 22;90(4):695-705
9288749
Nat Neurosci. 2006 Apr;9(4):511-8
16520734
WormBook. 2005 Dec 01;:1-22
18050408
Dev Cell. 2006 Mar;10(3):367-77
16516839
Genetics. 2006 Feb;172(2):893-913
16204220
Eur J Biochem. 1989 Oct 20;185(1):41-50
2806262
Neuron. 2003 Jan 9;37(1):53-65
12526772
J Cell Biol. 2007 Nov 19;179(4):761-75
17998398
Development. 2006 May;133(9):1757-66
16571624
Neuron. 2002 May 16;34(4):563-76
12062040
Dev Genet. 1990;11(1):49-64
2361334
Genetics. 2008 Jul;179(3):1357-71
18622031
Nat Cell Biol. 2007 Dec;9(12):1347-59
18026093
RNA. 2002 Jun;8(6):725-39
12088146
J Neurosci. 2008 Mar 26;28(13):3456-67
18367611
Dev Biol. 1985 Sep;111(1):158-70
3928418
PLoS Biol. 2010 Feb 02;8(2):e1000297
20126385
Annu Rev Neurosci. 2009;32:347-81
19400726
Mol Biol Cell. 1998 Aug;9(8):2157-71
9693373
Neuron. 2007 Nov 8;56(3):441-55
17988629
Eur J Biochem. 1987 Sep 15;167(3):441-8
2820726
Development. 1997 May;124(9):1831-43
9165130
Development. 2009 Apr;136(7):1201-10
19244282
Genetics. 1991 Sep;129(1):79-94
1936965
Cell. 1990 Nov 30;63(5):895-905
2257628
Neuron. 1992 Feb;8(2):307-22
1739461
Dev Biol. 2005 Sep 15;285(2):447-61
16109397
Genetics. 2004 Jul;167(3):1165-76
15280232
Nat Cell Biol. 2000 Mar;2(3):131-6
10707082
Cell. 1996 Oct 18;87(2):227-39
8861907
Development. 1996 Nov;122(11):3509-18
8951066
PLoS Biol. 2009 Apr 28;7(4):e99
19402756
Cell. 1993 Jul 16;74(1):29-42
8101474
Science. 1990 May 18;248(4957):857-60
2188361
Curr Biol. 2008 Jun 3;18(11):808-13
18499456
Annu Rev Cell Dev Biol. 2003;19:541-64
14570581
EMBO J. 1995 Jan 3;14(1):19-27
7828592
Genes Dev. 1995 Mar 1;9(5):521-33
7535279
Genetics. 1983 Aug;104(4):619-47
11813735
Cell. 2000 Jun 23;101(7):717-28
10892743
Curr Biol. 2007 Oct 23;17(20):1791-6
17935994
Curr Opin Cell Biol. 2002 Feb;14(1):88-103
11792550
Philos Trans R Soc Lond B Biol Sci. 1976 Aug 10;275(938):327-48
8806