FIGQY phosphorylation defines discrete populations of L1 cell adhesion molecules at sites of cell-cell contact and in migrating neurons.
Phosphorylation of neurofascin, a member of the L1 family of cell adhesion molecules (L1 CAMs), at the conserved FIGQY-tyrosine abolishes the ankyrin-neurofascin interaction. This study provides the first evidence, in Drosophila melanogaster and vertebrates, for the physiological occurrence of FIGQY phosphorylation in L1 family members. FIGQY tyrosine phosphorylation is localized at specialized cell junctions, including paranodes of sciatic nerve, neuromuscular junctions of adult rats and Drosophila embryos, epidermal muscle attachment sites of Drosophila, and adherens junctions of developing epithelial cells of rat and Drosophila. In addition, FIGQY-phosphorylated L1 CAMs are abundantly expressed in regions of neuronal migration and axon extension, including the embryonic cortex, the neonatal cerebellum and the rostral migratory stream, a region of continued neurogenesis and migration throughout adulthood in the rat. Based on our results, physiological FIGQY-tyrosine phosphorylation of the L1 family likely regulates adhesion molecule-ankyrin interactions establishing ankyrin-free and ankyrin-containing microdomains and participates in an ankyrin-independent intracellular signaling pathway at specialized sites of intercellular contact in epithelial and nervous tissue.
Jenkins
S M
SM
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. s.jenkins@cellbio.duke.edu
Kizhatil
K
K
Kramarcy
N R
NR
Sen
A
A
Sealock
R
R
Bennett
V
V
D022005:Adherens Junctions / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001665:Binding Sites; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D017487:Ankyrins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D019006:Neural Cell Adhesion Molecules; C504594:Nfasc protein, rat; D010455:Peptides; C061745:Nrg protein, Drosophila; D014443:Tyrosine