REGULATION OF MAP-2 INTERACTIONS WITH MICROTUBULES
MAP-2
assists in the creation of a functionally differentiated cytoplasm (within
the cell body, axons, and dendrites of neurons) by promoting the assembly
and stability of microtubules (MTs)
[OMIM].
MAP-2b and MAP-2c are found exclusively in embryonic axons, whereas MAP-2a
and MAP-2b are observed in dendrites of adult central nervous system neurons.
Except for the high-affinity binding interaction of MAP-2 (at a site near
its N-terminus) with the RII regulatory subunit of protein kinase A, all
other MAP-2 interactions (i.e., those with microtubules, neurofilaments,
F-actin, calmodulin, and phospholipids) appear to involve the so-called
microtubule-binding region
(MTBR)
comprising about 200 or so residues immediately prior to the MAP-2
carboxy-terminus. Accordingly, we have focused on this functionally versatile
MT-binding region as a means for approaching our long-term goal of using
knowledge of MAP-2 structure-function to elucidate MAP-2 role(s) in neurons.
To be further tested in this research project is the overall hypothesis that
phosphorylation at specific sites within the MT-binding regions of MAP-2
regulates one or more interactions of this microtubule-associated protein
to interact with other cytomatrix components. While our previous work dealt
with bovine MAP-2, this research proposal focuses on rat MAP 2c to facilitate
investigation of developing rat brain and rat neuronal cell lines. We should
note that rat and bovine MTBR primary structures are virtually identical,
and the two can be readily inter-converted by site directed mutagenesis at
fewer than six amino acid residues.