Proteolytic cleavage of the neural cell adhesion molecule by ADAM17/TACE is involved in neurite outgrowth.
Standard
Proteolytic cleavage of the neural cell adhesion molecule by ADAM17/TACE is involved in neurite outgrowth. / Kalus, Ina; Bormann, Ulrich; Mzoughi, Mounir; Schachner, Melitta; Kleene, Ralf.
In: J NEUROCHEM, Vol. 98, No. 1, 1, 2006, p. 78-88.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Proteolytic cleavage of the neural cell adhesion molecule by ADAM17/TACE is involved in neurite outgrowth.
AU - Kalus, Ina
AU - Bormann, Ulrich
AU - Mzoughi, Mounir
AU - Schachner, Melitta
AU - Kleene, Ralf
PY - 2006
Y1 - 2006
N2 - The transmembrane and multidomain neural cell adhesion molecule (NCAM) plays important functional roles in the developing and adult nervous system. NCAM is proteolytically processed and appears in soluble forms in the cerebrospinal fluid and in serum under normal and pathological conditions. In this report, we present evidence that the metalloprotease a disintegrin and a metalloprotease (ADAM)17/tumour necrosis factor alpha converting enzyme (TACE) cleaves the polysialylated as well as the non-polysialylated transmembrane isoforms of NCAM, whereas the glycophosphatidylinositol-linked isoform of NCAM is not proteolytically cleaved. A truncated, enzymatically inactive mutant of TACE did not result in release of the NCAM110 cleavage product. Proteolytic cleavage was enhanced by a calmodulin-specific inhibitor and the actin-destabilizing agents cytochalasin D and latrunculin B. In contrast, the microtubule-stabilizing agent colchicine or microtubule-destabilizing agent paclitaxel did not affect the release of the 110-kDa fragment of NCAM. Neurite outgrowth from cerebellar microexplants was inhibited in the presence of the metalloprotease inhibitor GM 6001 on substrate-coated NCAM, but not on poly-l-lysine. Upon transfection of hippocampal neurones with an enzymatically inactive mutant of TACE, NCAM-stimulated neurite outgrowth was inhibited without affecting neurite outgrowth on poly-l-lysine, showing that proteolytic processing of NCAM by the metalloprotease TACE is involved in NCAM-mediated neurite outgrowth.
AB - The transmembrane and multidomain neural cell adhesion molecule (NCAM) plays important functional roles in the developing and adult nervous system. NCAM is proteolytically processed and appears in soluble forms in the cerebrospinal fluid and in serum under normal and pathological conditions. In this report, we present evidence that the metalloprotease a disintegrin and a metalloprotease (ADAM)17/tumour necrosis factor alpha converting enzyme (TACE) cleaves the polysialylated as well as the non-polysialylated transmembrane isoforms of NCAM, whereas the glycophosphatidylinositol-linked isoform of NCAM is not proteolytically cleaved. A truncated, enzymatically inactive mutant of TACE did not result in release of the NCAM110 cleavage product. Proteolytic cleavage was enhanced by a calmodulin-specific inhibitor and the actin-destabilizing agents cytochalasin D and latrunculin B. In contrast, the microtubule-stabilizing agent colchicine or microtubule-destabilizing agent paclitaxel did not affect the release of the 110-kDa fragment of NCAM. Neurite outgrowth from cerebellar microexplants was inhibited in the presence of the metalloprotease inhibitor GM 6001 on substrate-coated NCAM, but not on poly-l-lysine. Upon transfection of hippocampal neurones with an enzymatically inactive mutant of TACE, NCAM-stimulated neurite outgrowth was inhibited without affecting neurite outgrowth on poly-l-lysine, showing that proteolytic processing of NCAM by the metalloprotease TACE is involved in NCAM-mediated neurite outgrowth.
KW - Animals
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred C57BL
KW - Cricetinae
KW - Cricetulus
KW - Blotting, Western/methods
KW - Actins/metabolism
KW - ADAM Proteins/deficiency/metabolism
KW - Brain/cytology
KW - Calmodulin/metabolism
KW - Cerebellum/cytology
KW - Metalloproteases/pharmacology
KW - Molecular Biology/methods
KW - Neural Cell Adhesion Molecules/metabolism
KW - Neurites/drug effects/physiology
KW - Neuroblastoma
KW - Neurons/cytology/drug effects/physiology
KW - Transfection/methods
KW - Animals
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred C57BL
KW - Cricetinae
KW - Cricetulus
KW - Blotting, Western/methods
KW - Actins/metabolism
KW - ADAM Proteins/deficiency/metabolism
KW - Brain/cytology
KW - Calmodulin/metabolism
KW - Cerebellum/cytology
KW - Metalloproteases/pharmacology
KW - Molecular Biology/methods
KW - Neural Cell Adhesion Molecules/metabolism
KW - Neurites/drug effects/physiology
KW - Neuroblastoma
KW - Neurons/cytology/drug effects/physiology
KW - Transfection/methods
M3 - SCORING: Journal article
VL - 98
SP - 78
EP - 88
JO - J NEUROCHEM
JF - J NEUROCHEM
SN - 0022-3042
IS - 1
M1 - 1
ER -
