+ TIPs
Microtubule-plus-end binding proteins (+ TIPs) are a subgroup of microtubule-associated proteins (MAPs) and affect cellular structures of microtubules . Attachment points for this large group of proteins arise at growing microtubule ends . They only bind to growing microtubule ends and link them to cellular structures.
construction
+ TIPs are made up of several protein domains and / or subunits and vary in size from a few hundred to thousands of amino acids . The first + TIP protein discovered was CLIP1 , a protein that makes cytoplasmic connections. In experiments with time-lapse recordings, it was noticed by fluorescent lines from the center of the cell to the outside. In the course of numerous subsequent studies, more than 20 different + TIP families were identified. They can be membrane-bound, in the cytoplasm, or as motor proteinsoccur and are divided into different classes based on their structures. There are also + TIP proteins that cannot be assigned to any of these classes. Their special structures enable the + TIPs to interact with other units; some + TIPs also combine properties of several classes.
function
+ TIPs are responsible in the cell for the construction and regulation of the interaction between microtubules and cellular structures such as vesicles , actin filaments , kinetochores and cell membranes . They can mutually influence their activity, strengthen and weaken binding affinities and be part of a larger protein complex , for example a motor protein.
Classification
The structure varies depending on the task of the respective + TIP protein. Most + TIPs can therefore be divided into different classes, but there are also some that cannot be clearly assigned due to the combined properties of several classes. In addition to EB proteins , which bind to the ends of the microtubules and thus build and maintain the network of protein-protein interactions , there are other + TIP proteins. + TIPs with CAP-Gly domains, with SxIP motifs and with TOG domains regulate the growth and binding affinities of other + TIPs and other proteins.
Models for the detection of the microtubule ends
The subject of numerous research work is the process of recognizing growing microtubule ends of the + TIPs. In some experiments + TIPs were observed which found the binding site on the microtubules autonomously without additional factors. Others need additional proteins to locate the growing ends. The exact component in the + TIPs that registers the growing ends is still unknown, but it is assumed that the GTP cap contained there plays a role. Another model are autonomously searching + TIPs that co-polymerize with tubulin subunits and thus find growing ends, but experiments did not provide any evidence for this. Most + TIPs require auxiliary factors, for example some travel via microtubule-bound EB proteins. Others recognize complex attachment sites that contain tubulin and EB proteins. This “search and capture” model, which already exists for other proteins, was further confirmed by the discovery of + TIPs as essential links. The "fast exchange" model describes a rapid association and dissociation of proteins on the microtubules, which was demonstrated by fluorescence experiments with iFRAP. This change at growing ends guarantees a large number of binding proteins in a short time.
Individual evidence
- ↑ a b c d e f cell.com: Plus-End-Tracking Proteins and Their Interactions at Microtubule Ends , last accessed January 22, 2016.
- ↑ a b c d Julia Arens: The role of microtubule-regulating proteins during neuronal differentiation , 2012, Technical University Dortmund, Max Planck Institute for Molecular Physiology.