Journal Article

Proteome analysis of microtubule-associated proteins and their interacting partners from mammalian brain

Kroening, Mario, Koehler, Christian J., Thiede, Bernd, Kozielski, Frank, Panse, Isabel, Donaldson, Ian M., DeBonis, Salvatore, Riaz, Tahira, Strozynski, Margarita

2011

Overview

The microtubule (MT) cytoskeleton is essential for a variety of cellular processes. MTs are finely regulated by distinct classes of MT-associated proteins (MAPs), which themselves bind to and are regulated by a large number of additional proteins. We have carried out proteome analyses of tubulin-rich and tubulin-depleted MAPs and their interacting partners isolated from bovine brain. In total, 573 proteins were identified giving us unprecedented access to brain-specific MT-associated proteins from mammalian brain. Most of the standard MAPs were identified and at least 500 proteins have been reported as being associated with MTs. We identified protein complexes with a large number of subunits such as brain-specific motor/adaptor/cargo complexes for kinesins, dynein, and dynactin, and proteins of an RNA-transporting granule. About 25% of the identified proteins were also found in the synaptic vesicle proteome. Analysis of the MS/MS data revealed many posttranslational modifications, amino acid changes, and alternative splice variants, particularly in tau, a key protein implicated in Alzheimer’s disease. Bioinformatic analysis of known protein–protein interactions of the identified proteins indicated that the number of MAPs and their associated proteins is larger than previously anticipated and that our database will be a useful resource to identify novel binding partners.

• Publisher: Springer Vienna,Springer Nature B.V
• Subject: Alternative splicing / Alzheimer's disease / Amino Acid Sequence / Amino acids / Analytical Chemistry / Animals / Biochemical Engineering / Biochemistry / bioinformatics / Biomedical and Life Sciences / Brain / Brain - metabolism / Cattle / Cytoskeleton / Dynactin / Dynein / dynein ATPase / Humans / kinesin / Life Sciences / Mammals / Microtubule-associated proteins / microtubules / Microtubules - metabolism / Molecular Sequence Data / Molecular Weight / Neurobiology / Neurodegenerative diseases / Original Article / Phosphoproteins - chemistry / Phosphoproteins - isolation & purification / Phosphoproteins - metabolism / Protein interaction / Protein Interaction Mapping / Protein Isoforms - metabolism / Protein Processing, Post-Translational / Protein transport / Proteins / proteome / Proteome - metabolism / Proteomes / Proteomics / synaptic vesicles / Tandem Mass Spectrometry / Tau protein / Tubulin / Tubulin - metabolism