unc-44 Ankyrin and stn-2 gamma-syntrophin regulate sax-7 L1CAM function in maintaining neuronal positioning in Caenorhabditis elegans.
The L1 family of single-pass transmembrane cell adhesion molecules (L1CAMs) is conserved from Caenorhabditis elegans and Drosophila to vertebrates and is required for axon guidance, neurite outgrowth, and maintenance of neuronal positions. The extracellular region of L1CAMs mediates cell adhesion via interactions with diverse cell-surface and extracellular matrix proteins. In contrast, less is known regarding the function of the intracellular domains in the L1CAM cytoplasmic tail. Previously, we identified a role of the C. elegans L1CAM homolog, SAX-7, in maintaining neuronal and axonal positioning. Here, we demonstrate that this function is dependent on three conserved motifs that reside in the SAX-7 cytoplasmic tail: (1) the FERM-binding motif, (2) the ankyrin-binding domain, and (3) the PDZ-binding motif. Furthermore, we provide molecular and genetic evidence that UNC-44 ankyrin and STN-2 gamma-syntrophin bind SAX-7 via the respective ankyrin-binding and PDZ-binding motifs to regulate SAX-7 function in maintaining neuronal positioning.
Zhou
Shan
S
Department of Genetics, Cell Biology and Development, Developmental Biology Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Opperman
Karla
K
Wang
Xuelin
X
Chen
Lihsia
L
D000818:Animals; D030801:Animals, Genetically Modified; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D054792:Muscle, Striated / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D012518:Sarcomeres / Q000502:physiology; D020798:Two-Hybrid System Techniques
D017487:Ankyrins; D029742:Caenorhabditis elegans Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; C501528:SAX-7 protein, C elegans; C479074:stn-1 protein, C elegans; C093514:unc-44 protein, C elegans
J Cell Biol. 1997 May 5;137(3):703-14
9151675
Dev Biol. 1985 Sep;111(1):158-70
3928418
Cell. 1992 Mar 20;68(6):1061-75
1547503
Eur J Hum Genet. 1995;3(5):273-84
8556302
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12957-62
9371782
Nature. 1997 Oct 23;389(6653):870-6
9349821
J Biol Chem. 2003 Jan 17;278(3):1915-23
12429735
Dev Cell. 2004 Jun;6(6):865-73
15177034
Genetics. 1995 Nov;141(3):977-88
8582641
J Cell Biol. 2008 Jan 14;180(1):233-46
18195110
Nat Rev Mol Cell Biol. 2002 Aug;3(8):586-99
12154370
J Cell Biol. 1995 May;129(4):1127-41
7744961
J Biol Chem. 2001 Apr 6;276(14):10646-54
11152476
Genetics. 1998 Jul;149(3):1323-34
9649523
J Mol Biol. 2003 Oct 3;332(5):1037-46
14499607
J Biol Chem. 2000 May 26;275(21):15851-60
10747910
J Neurosci. 2002 Sep 15;22(18):7948-58
12223548
Mol Cell Neurosci. 2006 Dec;33(4):441-6
17045809
Front Biosci. 2003 Sep 01;8:s1210-25
12957823
Mol Genet Genomics. 2002 May;267(3):291-302
12073031
J Mol Biol. 2001 Mar 16;307(1):107-17
11243807
Development. 2001 Oct;128(20):4079-92
11641230
Mol Cell Neurosci. 2008 Jan;37(1):56-68
17933550
Dev Biol. 2004 Aug 1;272(1):262-76
15242805
Development. 1994 Aug;120(8):2175-86
7925019
Mol Cell Neurosci. 2000 Jan;15(1):1-10
10662501
J Biol Chem. 1998 Nov 13;273(46):30785-94
9804856
Development. 1999 Aug;126(16):3679-92
10409513
Dev Biol. 2005 Aug 15;284(2):273-91
16023097
Curr Biol. 2006 Aug 22;16(16):1678-83
16920632
Neurosignals. 2002 May-Jun;11(3):123-9
12138249
Genetics. 1974 May;77(1):71-94
4366476
J Cell Biol. 2001 Aug 20;154(4):841-55
11502758
Neurogenetics. 1998 Dec;2(1):61-72
9933302
EMBO J. 2005 Apr 6;24(7):1477-88
15775964
J Cell Biol. 1998 Nov 30;143(5):1305-15
9832558
J Cell Biol. 2002 Jun 24;157(7):1105-12
12070130
J Cell Sci. 2001 Nov;114(Pt 21):3823-35
11719549
J Biol Chem. 1994 Nov 4;269(44):27163-6
7961622
Sci STKE. 2003 Apr 22;2003(179):RE7
12709532
Hum Mutat. 2001;18(1):1-12
11438988
J Cell Biol. 1995 May;129(4):1081-92
7744957
Science. 1998 Jul 31;281(5377):706-9
9685266
J Biol Chem. 2001 Jul 13;276(28):26526-33
11352924