The interaction between cell adhesion molecule L1, matrix metalloproteinase 14, and adenine nucleotide translocator at the plasma membrane regulates L1-mediated neurite outgrowth of murine cerebellar neurons.
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The interaction between cell adhesion molecule L1, matrix metalloproteinase 14, and adenine nucleotide translocator at the plasma membrane regulates L1-mediated neurite outgrowth of murine cerebellar neurons. / Loers, Gabriele; Makhina, Tatjana; Bork, Ute; Dörner, Andrea; Schachner, Melitta; Kleene, Ralf.
in: J NEUROSCI, Jahrgang 32, Nr. 11, 11, 2012, S. 3917-3930.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The interaction between cell adhesion molecule L1, matrix metalloproteinase 14, and adenine nucleotide translocator at the plasma membrane regulates L1-mediated neurite outgrowth of murine cerebellar neurons.
AU - Loers, Gabriele
AU - Makhina, Tatjana
AU - Bork, Ute
AU - Dörner, Andrea
AU - Schachner, Melitta
AU - Kleene, Ralf
PY - 2012
Y1 - 2012
N2 - We have identified the adenine nucleotide translocator (ANT) isoforms ANT1 and ANT2 that are present in the plasma membrane of mouse cerebellar neurons as novel binding partners of the cell adhesion molecule L1. The direct interaction between ANT and L1 is mediated by sites within the fibronectin type III domains of L1 and the first and third extracellular loops of the ANT proteins. We also show that L1 interacts with the ANT binding partner matrix metalloprotease 14 (MMP14) and that the ANT proteins bind directly to the L1 interaction partner glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Moreover, we provide evidence that the functional interplay between L1, ANT proteins, MMP14, and GAPDH at the plasma membrane mediates L1-induced neurite outgrowth of cerebellar neurons. Disruption of this interplay by ANT inhibitors, ANT-derived synthetic peptides, and/or function-blocking MMP14 and ANT antibodies leads to alterations in L1-dependent neurite outgrowth. Stimulation of L1-mediated signaling in cerebellar neurons triggers transient ATP secretion via ANT proteins and leads to transient src family-dependent tyrosine phosphorylation of L1, ANT1, ANT2, and MMP14. Thus, our results indicate that plasma membrane-localized ANT1 and ANT2 regulate L1-mediated neurite outgrowth in conjunction with MMP14.
AB - We have identified the adenine nucleotide translocator (ANT) isoforms ANT1 and ANT2 that are present in the plasma membrane of mouse cerebellar neurons as novel binding partners of the cell adhesion molecule L1. The direct interaction between ANT and L1 is mediated by sites within the fibronectin type III domains of L1 and the first and third extracellular loops of the ANT proteins. We also show that L1 interacts with the ANT binding partner matrix metalloprotease 14 (MMP14) and that the ANT proteins bind directly to the L1 interaction partner glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Moreover, we provide evidence that the functional interplay between L1, ANT proteins, MMP14, and GAPDH at the plasma membrane mediates L1-induced neurite outgrowth of cerebellar neurons. Disruption of this interplay by ANT inhibitors, ANT-derived synthetic peptides, and/or function-blocking MMP14 and ANT antibodies leads to alterations in L1-dependent neurite outgrowth. Stimulation of L1-mediated signaling in cerebellar neurons triggers transient ATP secretion via ANT proteins and leads to transient src family-dependent tyrosine phosphorylation of L1, ANT1, ANT2, and MMP14. Thus, our results indicate that plasma membrane-localized ANT1 and ANT2 regulate L1-mediated neurite outgrowth in conjunction with MMP14.
KW - Animals
KW - Male
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred C57BL
KW - Protein Binding/physiology
KW - Adenine Nucleotide Translocator 1/metabolism
KW - Adenine Nucleotide Translocator 2/metabolism
KW - Cerebellum/cytology/metabolism
KW - Matrix Metalloproteinase 14/metabolism
KW - Membrane Proteins/metabolism/physiology
KW - Neural Cell Adhesion Molecule L1/physiology
KW - Neurites/physiology
KW - Neurons/metabolism
KW - Animals
KW - Male
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred C57BL
KW - Protein Binding/physiology
KW - Adenine Nucleotide Translocator 1/metabolism
KW - Adenine Nucleotide Translocator 2/metabolism
KW - Cerebellum/cytology/metabolism
KW - Matrix Metalloproteinase 14/metabolism
KW - Membrane Proteins/metabolism/physiology
KW - Neural Cell Adhesion Molecule L1/physiology
KW - Neurites/physiology
KW - Neurons/metabolism
M3 - SCORING: Journal article
VL - 32
SP - 3917
EP - 3930
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 11
M1 - 11
ER -
