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Michel O. Steinmetz, Paul Scherrer Institute, Villigen-PSI, Switzerland
([email protected])
Molecular mechanisms of microtubule plus-end tracking protein (+TIPs)
Microtubule plus-end tracking proteins (+TIPs) are specialized microtubule-associated
proteins that are conserved in all eukaryotes. They are characterized by their
preferential accumulation at growing microtubule plus ends. +TIPs regulate microtubule
dynamics and mediate the anchorage of microtubules to different cellular structures,
including kinetochores and membrane compartments. As such, they play important
roles in all microtubule-based cellular processes. +TIPs comprise a structurally and
functionally diverse group of multidomain and/or multisubunit proteins, ranging in size
from a few hundred up to thousands of residues. An important feature of +TIPs is their
remarkable ability to form dynamic interaction networks at growing microtubule ends.
In this context, the members of the evolutionary conserved end binding protein (EB)
family act as master regulators of +TIP networks. EBs are able to autonomously track
microtubule tips independently of any binding partner, while most of the remaining
+TIPs generally require EBs to efficiently localize to growing microtubule ends. In my
lecture I will discuss the molecular mechanisms used by +TIPs to get access to growing
microtubule tips.
Reading:
1. Akhmanova A. and Steinmetz M.O. (2010). Microtubule +TIPs at a glance. J Cell
Sci. 123: 3415-3419.
2. Hayashi I., Plevin M.J., and Ikura M. (2007). CLIP170 autoinhibition mimics
intermolecular interactions with p150Glued or EB1. Nat. Struct. Mol. Biol. 14:
980-981.
3. Honnappa S., Okhrimenko O., Jaussi R., Jawhari H., Jelesarov I., Winkler F.K., and
Steinmetz M.O. (2006). Key interaction modes of dynamic +TIP networks. Mol.
Cell 23: 663-671.
4. Honnappa S., Gouveia S.M., Weisbrich A., Damberger F.F., Bhavesh N.S., Jawhari
H., Grigoriev I., van Rijssel F.J., Buey R.M., Lawera A. et al. (2009). An EB1-binding
motif acts as a microtubule tip localization signal. Cell 138: 366-376.
5. Steinmetz M.O. and Akhmanova A. (2008). Capturing protein tails by CAP-Gly
domains. Trends Biochem. Sci. 33: 535-545.
6. Weisbrich A., Honnappa S., Jaussi R., Okhrimenko O., Frey D., Jelesarov I.,
Akhmanova A., and Steinmetz M.O. (2007). Structure-function relationship of
CAP-Gly domains. Nat. Struct. Mol. Biol. 14: 959-967.
7. Mishima M., Maesaki R., Kasa M., Watanabe T., Fukata M., Kaibuchi K., and
Hakoshima T. (2007). Structural basis for tubulin recognition by cytoplasmic
linker protein 170 and its autoinhibition. Proc. Natl. Acad. Sci. U. S. A 104: 1034610351.
8. Bieling P., Kandels-Lewis S., Telley I.A., van D.J., Janke C., and Surrey T. (2008).
CLIP-170 tracks growing microtubule ends by dynamically recognizing
composite EB1/tubulin-binding sites. J Cell Biol. 183: 1223-1233.
9. Maurer S.P., Fourniol F.J., Bohner G., Moores C.A., and Surrey T. (2012). EBs
recognize a nucleotide-dependent structural cap at growing microtubule ends.
Cell 149: 371-382.
10. Kumar P. and Wittmann T. (2012). +TIPs: SxIPping along microtubule ends.
Trends Cell Biol. 22: 418-428.