Protein family review
This in an extract of a protein family review which first appeared in GenomeBiology, and is reproduced by permission of the publisher, BioMedCentral Ltd.
Authors:
Department of Cell Biology, The Scripps Research Institute and Institute for Childhood and Neglected Diseases, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
Correspondence:
Shelley Halpain.
Email:
shelley@scripps.edu
Read the full article
Subscribers to GenomeBiology may view the full version of this review article online at www.genomebiology.com
Published:
23 December 2004
The MAP2/Tau family of microtubule-associated proteins
Summary
Microtubule-associated proteins (MAPs) of the MAP2/Tau family include the vertebrate proteins MAP2, MAP4, and Tau and homologs in other animals. All three vertebrate members of the family have alternative splice forms; all isoforms share a conserved carboxy-terminal domain containing microtubule-binding repeats, and an amino-terminal projection domain of varying size. MAP2 and Tau are found in neurons, whereas MAP4 is present in many other tissues but is generally absent from neurons. Members of the family are best known for their microtubule-stabilizing activity and for proposed roles regulating microtubule networks in the axons and dendrites of neurons. Contrary to this simple, traditional view, accumulating evidence suggests a much broader range of functions, such as binding to filamentous (F) actin, recruitment of signaling proteins, and regulation of microtubule-mediated transport. Tau is also implicated in Alzheimer's disease and other dementias. The ability of MAP2 to interact with both microtubules and F-actin might be critical for neuromorphogenic processes, such as neurite initiation, during which networks of microtubules and F-actin are reorganized in a coordinated manner. Various upstream kinases and interacting proteins have been identified that regulate the microtubule-stabilizing activity of MAP2/Tau family proteins.
Frontiers
Since their original identification over 20 years ago, classical structural MAPs of the MAP2/Tau family have been extensively characterized in vitro and in vivo. A major challenge for further illuminating their function is the vast number of interaction partners and protein kinases predicted and confirmed to phosphorylate MAP2/Tau proteins. Although some key pathways controlling their activity have been elucidated, a broader and more precise analysis of phosphorylation and other post-translational modifications is needed to fully understand MAP2/Tau protein function in signaling networks controlling the morphogenesis of neurons. Recent progress in understanding the molecular mechanisms underlying MAP-microtubule and MAP-actin interactions in vitro is promising, but biological functions remain elusive. Future studies will need to correlate the effects of MAP2/Tau proteins in vivo with molecular knowledge gained from in vitro analyses. The apparent functional redundancies and cross-talk with other MAPs and cytoskeletal regulators are challenges that will require creative experimental strategies if we are to elucidate the specific functions of MAP2/Tau family proteins in cytoskeletal organization and morphological change.
© BioMedCentral Ltd. Protein family reviews appear as regular features in GenomeBiology. A complete list of protein family reviews is available online at http://genomebiology.com/proteinfamilyreviews/
Phylogenetic analysis of MAP2/Tau family proteins
The domain organization of MAP2/Tau family proteins