Microtubule-associated protein 1A (MAP1A) and MAP1B: light chains determine distinct functional properties.
The microtubule-associated proteins 1A (MAP1A) and 1B (MAP1B) are distantly related protein complexes consisting of heavy and light chains and are thought to play a role in regulating the neuronal cytoskeleton, MAP1B during neuritogenesis and MAP1A in mature neurons. To elucidate functional differences between MAP1B and MAP1A and to determine the role of the light chain in the MAP1A protein complex, we chose to investigate the functional properties of the light chain of MAP1A (LC2) and compare them with the light chain of MAP1B (LC1). We found that LC2 binds to microtubules in vivo and in vitro and induces rapid polymerization of tubulin. A microtubule-binding domain in its NH(2) terminus was found to be necessary and sufficient for these activities. The analysis of LC1 revealed that it too bound to microtubules and induced tubulin polymerization via a crucial but structurally unrelated NH(2)-terminal domain. The two light chains differed, however, in their effects on microtubule bundling and stability in vivo. Furthermore, we identified actin filament binding domains located at the COOH terminus of LC2 and LC1 and obtained evidence that binding to actin filaments is attributable to direct interaction with actin. Our findings establish LC2 as a crucial determinant of MAP1A function, reveal LC2 as a potential linker of neuronal microtubules and microfilaments, and suggest that the postnatal substitution of MAP1B by MAP1A leads to expression of a protein with an overlapping but distinct set of functions.
Noiges
Rainer
R
Institute of Biochemistry and Molecular Cell Biology, Vienna Biocenter, University of Vienna, A-1030 Vienna, Austria.
Eichinger
Rene
R
Kutschera
Waltraud
W
Fischer
Irmgard
I
Nemeth
Zsuzsanna
Z
Wiche
Gerhard
G
Propst
Friedrich
F
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D046911:Macromolecular Substances; D007614:Macropodidae; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits; D051381:Rats; D013329:Structure-Activity Relationship; D014162:Transfection; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
D046911:Macromolecular Substances; C490546:Map1a protein, rat; D008869:Microtubule-Associated Proteins; D021122:Protein Subunits; D014404:Tubulin; C085284:microtubule-associated protein 1B; D015739:Nocodazole