MAP2c, but not tau, binds and bundles F-actin via its microtubule binding domain.
BACKGROUND
MAP2 and tau are abundant microtubule-associated proteins (MAPs) in neurons. The development of neuronal dendrites and axons requires a dynamic interaction between microtubules and actin filaments. MAPs represent good candidates to mediate such interactions. Although MAP2c and tau have similar, well-characterized microtubule binding activities, their actin interaction is poorly understood.


RESULTS
Here, we show by using a cosedimentation assay that MAP2c binds F-actin. Upon actin binding, MAP2c organizes F-actin into closely packed actin bundles. Moreover, we show by using a deletion approach that MAP2c's microtubule binding domain (MTBD) is both necessary and sufficient for both F-actin binding and bundling activities. Surprisingly, even though the MAP2 and tau MTBDs share high sequence homology and possess similar microtubule binding activities, tau is unable to bind or bundle F-actin. Furthermore, experiments with chimeric proteins demonstrate that the actin binding activity fully correlates with the ability to promote neurite initiation in neuroblastoma cells.


CONCLUSIONS
These results provide the first demonstration that the MAP2c and tau MTBD domains exhibit distinct properties, diverging in actin binding and neurite initiation activities. These results implicate a novel actin function for MAP2c in neuronal morphogenesis and furthermore suggest that actin interactions could contribute to functional differences between MAP2 and tau in neurons.
Roger
Benoit
B
Department of Cell Biology and Institute for Childhood and Neglected Diseases, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Al-Bassam
Jawdat
J
Dehmelt
Leif
L
Milligan
Ronald A
RA
Halpain
Shelley
S
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D002498:Centrifugation; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009024:Morphogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D000199:Actins; D017931:DNA Primers; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D016875:tau Proteins