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Microtubule Plus-End Tracking by CLIP-170
Requires EB1.
Proc. Nat. Acad. Sci. 106:492-497. 2009.
Plus-end tracking proteins ('+TIPs') are a special class
of microtubule-associated proteins that associate with the
growing ends of microtubules {1}. Because many of these proteins
interact with tubulin and with each other, it has been difficult
to determine the precise mechanisms of how they localize to
the growing microtubule end. Two opposing models have been:
on one hand, the 'copolymerization' model, in which +TIPs
bound to tubulin dimer incorporate into the microtubule lattice
as a single molecular entity, with the +TIPs dissociating
at some point afterwards, and, on the other hand, the 'end-recognition'
model, in which +TIPs bind to the growing lattice by recognizing
structural features (i.e. tubulin subunit conformations) that
are unique to the tip of the lattice. This study, together
with other recent in vivo work {2}, comes down firmly on the
side of the latter model. Using purified proteins, the authors
show that EB1, probably the most conserved of all +TIPs, binds
autonomously to the growing microtubule end and also turns
over very quickly in repeated cycles of dissociation and rebinding.
By contrast, the 'founder' member of the +TIP proteins, CLIP-170,
shows similar tracking behavior and turnover in the presence
of EB1, but in the absence of EB1, CLIP-170 binds more uniformly
along the entire microtubule lattice, without any preference
for the growing ends. This is a 'textbook' study, with remarkably
clear results, and similar results have also been obtained
independently by another lab {3} (see evaluation). It is also
interesting that these results differ, in a biologically interesting
way, from those obtained in an earlier study using purified
fission yeast proteins {4}. The nature of the differences
suggests that the mechanisms involved in +TIP behavior are
likely not 'fundamentally' different in different biological
systems but rather that subtle modifications -- variations
on a core mechanism -- are likely to be responsible for what
might appear to be significant differences in vivo.
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