Caldendrin but not calmodulin binds to light chain 3 of MAP1A/B: an association with the microtubule cytoskeleton highlighting exclusive binding partners for neuronal Ca(2+)-sensor proteins.
Caldendrin is a neuronal Ca(2+)-sensor protein (NCS), which represents the closest homologue of calmodulin (CaM) in nerve cells. It is tightly associated with the somato-dendritic cytoskeleton of neurons and highly enriched in the postsynaptic cytomatrix. Here, we report that caldendrin specifically associates with the microtubule cytoskeleton via an interaction with light chain 3 (LC3), a microtubule component with sequence homology to the GABAA receptor-associated protein (GABARAP), which is, like LC3, probably involved in cellular transport processes. Interestingly, two binding sites exist in LC3 for caldendrin from which only one exhibits a strict Ca(2+)-dependency for the interaction to take place but both require the presence of the first two EF-hands of caldendrin. CaM, however, is not capable of binding to LC3 at both sites despite its high degree of primary structure similarity with caldendrin. Computer modelling suggests that this might be explained by an altered distribution of surface charges at the first two EF-hands rendering each molecule, in principle, specific for a discrete set of binding partners. These findings provide molecular evidence that NCS can transduce signals to a specific target interaction irrespective of Ca(2+)-concentrations and CaM-levels.
Seidenbecher
Constanze I
CI
AG Molecular Mechanisms of Plasticity, Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, Brenneckestr. 6 39118 Magdeburg, Germany.
Landwehr
Marco
M
Smalla
Karl-Heinz
KH
Kreutz
Martin
M
Dieterich
Daniela C
DC
Zuschratter
Werner
W
Reissner
Carsten
C
Hammarback
James A
JA
Böckers
Tobias M
TM
Gundelfinger
Eckart D
ED
Kreutz
Michael R
MR
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000378:metabolism; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017239:Paclitaxel / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012261:Ribonucleoproteins / Q000378:metabolism; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
D002135:Calcium-Binding Proteins; D002147:Calmodulin; C093429:MAP1A protein, human; C490546:Map1a protein, rat; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D012261:Ribonucleoproteins; C085284:microtubule-associated protein 1B; C085577:Ca2+-binding protein-1; D017239:Paclitaxel; D002118:Calcium