Microtubule plus-end-tracking proteins: mechanisms and functions

doi:10.1016/j.ceb.2004.11.001

Current Opinion in Cell Biology

Volume 17, Issue 1, February 2005, Pages 47-54

https://doi.org/10.1016/j.ceb.2004.11.001 Get rights and content

Microtubule plus-end-tracking proteins (+TIPs) are a diverse group of molecules that display dynamic accumulation at the distal ends of growing microtubules. Specific binding to the growing microtubule tip coupled with quick detachment from the older lattice, plus-end-directed transport, and association with other +TIPs can all contribute to this protein localisation. +TIPs act mainly as microtubule-stabilising factors and at the same time often link microtubule ends to various cellular structures, such as the cell cortex or kinetochores. Regulation of the activity of +TIPs has profound effects on the shape of the microtubule network and plays an essential role in cell division, motility and morphogenesis.

Introduction

The microtubule (MT) network, one of the major cytoskeletal systems of all eukaryotic cells, is a highly dynamic structure. MTs, hollow tubes made of tubulin dimers, can assemble and disassemble in vitro from their two ends: the slow-growing (minus) end and the fast-growing (plus) end. In living cells, the minus ends are often stabilised or serve as MT depolymerisation sites, while the plus ends explore the cellular space, switching rapidly between phases of growth and shrinkage, a behaviour called dynamic instability [1]. The plus end of a MT is therefore an important site that often determines its destiny. It is not surprising, therefore, that all eukaryotic cells possess a complex protein machinery that associates with the MT plus ends, regulating their dynamics or their interaction with other cellular structures. MT end-binding proteins can be divided into MT destabilising factors, which include Kin I kinesins (for review, see 2., 3.) and MT plus-end-tracking proteins (+TIPs) [4], which will be the main topic of this review.

Section snippets

Mechanisms of plus-end accumulation

+TIPs are a highly diverse group of MT-associated proteins, including both MT-dependent motors and non-motor proteins (Table 1). The distinguishing feature of +TIPs compared to other MT-associated proteins is their specific accumulation at the plus ends of growing MTs (Figure 1). This dynamic localisation (which has also been called ‘surfing’ on the plus ends; see 4., 5.) was initially discovered by observing the live behaviour of the CLIP-170–green fluorescent protein fusions, which appeared

Role of +TIPs in microtubule stabilisation and capture

By binding to the MT ends, +TIPs can influence the MT's structure and accessibility for interaction with other proteins. Therefore, most +TIPs have a role in the regulation of MT dynamics. The function of many +TIPs is associated with MT stabilisation. MTs can be stabilised dynamically (by reducing the frequency of catastrophes or promoting repeated rescues) or by being captured in a paused state. It should be emphasized that in some cases apparent pauses might actually represent very short

Conclusions and future directions

+TIPs are evolutionarily conserved proteins that concentrate at the MT plus ends, where they mostly promote MT stabilisation and the interaction of MTs with different cellular components. In addition, many +TIPs are present at the centrosomes or spindle pole bodies and may have important roles in anchoring and stabilising MT minus ends or even in MT nucleation (see [62] for discussion). This issue has received comparatively little attention and requires further study.

An understanding of the

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest
•• of outstanding interest

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Microtubule plus-end-tracking proteins: mechanisms and functions

Introduction

Section snippets

Mechanisms of plus-end accumulation

Role of +TIPs in microtubule stabilisation and capture

Conclusions and future directions

References and recommended reading

Cell

Trends Cell Biol

Cell

Cell

Curr Biol

EMBO Rep

Dev Cell

Nat Cell Biol

Oncogene

Trends Cell Biol

J Cell Sci

Cell

Neuron

J Cell Biol

Curr Biol

J Cell Biol

Nat Cell Biol

Mol Biol Cell

J Cell Biol

Genes Dev

Science

Microtubule polymerization dynamics

Annu Rev Cell Dev Biol

Dynamics and mechanics of the microtubule plus end

Nature

Unconventional motoring: an overview of the Kin C and Kin I kinesins

Traffic

EB1–microtubule interactions in Xenopus egg extracts: role of EB1 in microtubule stabilization and mechanisms of targeting to microtubules

Mol Biol Cell

Dynamic localization of CLIP-170 to microtubule plus ends is coupled to microtubule assembly

J Cell Biol

Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity

Nature

A role for regulated binding of p150Glued to microtubule plus ends in organelle transport

J Cell Biol

Characterization of functional domains of human EB1 family proteins

J Biol Chem

Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localisation

J Cell Biol

Targeted movement of cell end factors in fission yeast

Nat Cell Biol

Cell cycle control of kinesin-mediated transport of Bik1 (CLIP-170) regulates microtubule stability and dynein activation

Dev Cell

Accumulation of cytoplasmic dynein and dynactin at microtubule plus ends in Aspergillus nidulans is kinesin-dependent

Mol Biol Cell

The microtubule plus-end-tracking proteins mal3p and tip1p cooperate for cell-end targeting of interphase microtubules

Curr Biol

APC binds to the novel protein EB1

Cancer Res

A role for regulated binding of p150^Glued to microtubule plus ends in organelle transport