Functional dissection of the C. elegans cell adhesion molecule SAX-7, a homologue of human L1

Roger Pocock; Claire Y Bénard; Lawrence Shapiro; Oliver Hobert

doi:10.1016/j.mcn.2007.08.014

Functional dissection of the C. elegans cell adhesion molecule SAX-7, a homologue of human L1

Roger Pocock, Claire Y Bénard, Lawrence Shapiro, Oliver Hobert

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

48 Citationer (Scopus)

Abstract

Udgivelsesdato: 2008-Jan

Originalsprog	Engelsk
Tidsskrift	Molecular and Cellular Neuroscience
Vol/bind	37
Udgave nummer	1
Sider (fra-til)	56-68
Antal sider	12
ISSN	1044-7431
DOI	https://doi.org/10.1016/j.mcn.2007.08.014
Status	Udgivet - 2007
Udgivet eksternt	Ja

Bibliografisk note

Keywords: Animals; Animals, Genetically Modified; Ankyrins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Adhesion; Models, Molecular; Molecular Sequence Data; Mutation; Nerve Tissue Proteins; Neural Cell Adhesion Molecule L1; Neural Cell Adhesion Molecules; Neurons; Protein Binding; Protein Structure, Tertiary

Adgang til dokumentet

10.1016/j.mcn.2007.08.014

Citationsformater

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title = "Functional dissection of the C. elegans cell adhesion molecule SAX-7, a homologue of human L1",

abstract = "Cell adhesion molecules of the Immunoglobulin superfamily (IgCAMs) play important roles in neuronal development, homeostasis and disease. Here, we use an animal in vivo assay system to study the function of sax-7, the Caenorhabditis elegans homologue of the human L1 IgCAM, a homophilic adhesion molecule involved in several neurological diseases. We show that the 6 Ig/5 FnIII domain protein SAX-7 acts autonomously in the nervous system to maintain axon position in the ventral nerve cord of the nematode. As previously reported, sax-7 is also required to maintain the relative positioning of neuronal cell bodies in several head ganglia. We use the loss of cellular adhesiveness in sax-7 null mutants as an assay system to investigate the contribution of individual domains and sequence motifs to the function of SAX-7, utilizing transgenic rescue approaches. By shortening the hinge region between the Ig1+2 and Ig3+4 domains, we improve the adhesive function of SAX-7, thereby providing support for a previously proposed autoinhibitory {"}horseshoe{"} conformation of IgCAMs. However, we find that Ig3+4 are the only Ig domains required and sufficient for the adhesive function of SAX-7. Previous models of L1-type IgCAMs that invoke an important role of the first two Ig domains in controlling adhesion therefore do not appear to apply to SAX-7. Moreover, we find that neither the 5 FnIII domains, nor the protease cleavage site embedded in them, are required for the adhesive function of SAX-7. Lastly, we show that of the several protein binding motifs present in the intracellular region of SAX-7, only its ankyrin binding motif is required and also solely sufficient to confer the adhesive functions of SAX-7.",

author = "Roger Pocock and B{\'e}nard, {Claire Y} and Lawrence Shapiro and Oliver Hobert",

note = "Keywords: Animals; Animals, Genetically Modified; Ankyrins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Adhesion; Models, Molecular; Molecular Sequence Data; Mutation; Nerve Tissue Proteins; Neural Cell Adhesion Molecule L1; Neural Cell Adhesion Molecules; Neurons; Protein Binding; Protein Structure, Tertiary",

year = "2007",

doi = "10.1016/j.mcn.2007.08.014",

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T1 - Functional dissection of the C. elegans cell adhesion molecule SAX-7, a homologue of human L1

AU - Pocock, Roger

AU - Bénard, Claire Y

AU - Shapiro, Lawrence

AU - Hobert, Oliver

N1 - Keywords: Animals; Animals, Genetically Modified; Ankyrins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Adhesion; Models, Molecular; Molecular Sequence Data; Mutation; Nerve Tissue Proteins; Neural Cell Adhesion Molecule L1; Neural Cell Adhesion Molecules; Neurons; Protein Binding; Protein Structure, Tertiary

PY - 2007

Y1 - 2007

N2 - Cell adhesion molecules of the Immunoglobulin superfamily (IgCAMs) play important roles in neuronal development, homeostasis and disease. Here, we use an animal in vivo assay system to study the function of sax-7, the Caenorhabditis elegans homologue of the human L1 IgCAM, a homophilic adhesion molecule involved in several neurological diseases. We show that the 6 Ig/5 FnIII domain protein SAX-7 acts autonomously in the nervous system to maintain axon position in the ventral nerve cord of the nematode. As previously reported, sax-7 is also required to maintain the relative positioning of neuronal cell bodies in several head ganglia. We use the loss of cellular adhesiveness in sax-7 null mutants as an assay system to investigate the contribution of individual domains and sequence motifs to the function of SAX-7, utilizing transgenic rescue approaches. By shortening the hinge region between the Ig1+2 and Ig3+4 domains, we improve the adhesive function of SAX-7, thereby providing support for a previously proposed autoinhibitory "horseshoe" conformation of IgCAMs. However, we find that Ig3+4 are the only Ig domains required and sufficient for the adhesive function of SAX-7. Previous models of L1-type IgCAMs that invoke an important role of the first two Ig domains in controlling adhesion therefore do not appear to apply to SAX-7. Moreover, we find that neither the 5 FnIII domains, nor the protease cleavage site embedded in them, are required for the adhesive function of SAX-7. Lastly, we show that of the several protein binding motifs present in the intracellular region of SAX-7, only its ankyrin binding motif is required and also solely sufficient to confer the adhesive functions of SAX-7.

AB - Cell adhesion molecules of the Immunoglobulin superfamily (IgCAMs) play important roles in neuronal development, homeostasis and disease. Here, we use an animal in vivo assay system to study the function of sax-7, the Caenorhabditis elegans homologue of the human L1 IgCAM, a homophilic adhesion molecule involved in several neurological diseases. We show that the 6 Ig/5 FnIII domain protein SAX-7 acts autonomously in the nervous system to maintain axon position in the ventral nerve cord of the nematode. As previously reported, sax-7 is also required to maintain the relative positioning of neuronal cell bodies in several head ganglia. We use the loss of cellular adhesiveness in sax-7 null mutants as an assay system to investigate the contribution of individual domains and sequence motifs to the function of SAX-7, utilizing transgenic rescue approaches. By shortening the hinge region between the Ig1+2 and Ig3+4 domains, we improve the adhesive function of SAX-7, thereby providing support for a previously proposed autoinhibitory "horseshoe" conformation of IgCAMs. However, we find that Ig3+4 are the only Ig domains required and sufficient for the adhesive function of SAX-7. Previous models of L1-type IgCAMs that invoke an important role of the first two Ig domains in controlling adhesion therefore do not appear to apply to SAX-7. Moreover, we find that neither the 5 FnIII domains, nor the protease cleavage site embedded in them, are required for the adhesive function of SAX-7. Lastly, we show that of the several protein binding motifs present in the intracellular region of SAX-7, only its ankyrin binding motif is required and also solely sufficient to confer the adhesive functions of SAX-7.

U2 - 10.1016/j.mcn.2007.08.014

DO - 10.1016/j.mcn.2007.08.014

M3 - Journal article

C2 - 17933550

SN - 1044-7431

VL - 37

SP - 56

EP - 68

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

IS - 1

ER -