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The binding of MAP-2 and tau on brain microtubules in vitro: implications for microtubule structure
Abstract:
We have presented data that indicate that MAP-2 associates with brain microtubules at nonrandomly distributed sites, whose distribution on the microtubule polymer can best be described by the 12-dimer MAP superlattice originally described by Amos; because of the additional spacings, however, between MAP-2 projections observed on MAP-2-saturated microtubules, we suggest that the 6-dimer MAP superlattice, or what we will call the double Amos superlattice, more completely specifies the total set of MAP-binding sites on cytoplasmic microtubules. Second, we have shown that brain microtubules reassembled in vitro contain a heterogeneous population of MAP-binding sites, which differ in their affinities for the two MAPs, MAP-2 and tau. Third, we have shown that microtubule populations that differ in their MAP content have subtle, but detectable differences in their tubulin isotype composition. Based on all the data presented here, we have presented the idea of a nonrandom distribution of tubulin isotypes within a microtubule as a means by which a cell could specify both the identity and the distribution of MAP-binding sites.
Insights
Microtubule-associated protein 2 (MAP-2) binds to brain microtubules at specific sites, forming a double Amos superlattice. Differences in microtubule-associated proteins (MAPs) correlate with tubulin isotype composition, suggesting a role in MAP-binding site identity and distribution.
Area of Science:
- Cell Biology
- Biochemistry
- Structural Biology
Background:
- Microtubules are essential cytoskeletal components involved in various cellular processes.
- Microtubule-associated proteins (MAPs) regulate microtubule dynamics and organization.
- The precise binding sites and interactions of MAPs on microtubules are not fully understood.
Purpose of the Study:
- To investigate the distribution and binding characteristics of MAP-2 on brain microtubules.
- To explore the heterogeneity of MAP-binding sites and their affinity for different MAPs.
- To determine the relationship between MAP content, tubulin isotype composition, and MAP-binding site distribution.
Main Methods:
- Analysis of MAP-2 binding patterns on microtubules using superlattice models.
- In vitro reassembly of brain microtubules to assess MAP-binding site heterogeneity.
- Characterization of tubulin isotype composition in microtubules with varying MAP content.
Main Results:
- MAP-2 associates with microtubules at nonrandom sites, best described by a 6-dimer superlattice (double Amos superlattice).
- Reassembled microtubules exhibit heterogeneous MAP-binding sites with differential affinities for MAP-2 and tau.
- Microtubule populations with different MAP content show subtle but detectable variations in tubulin isotype composition.
Conclusions:
- The distribution of MAP-binding sites on cytoplasmic microtubules is specified by a double Amos superlattice.
- Heterogeneity in MAP-binding sites suggests differential affinities for various MAPs.
- Nonrandom distribution of tubulin isotypes within microtubules may dictate the identity and distribution of MAP-binding sites.