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Journal article
Resurrecting the Mysteries of Big Tau
Trends in neurosciences (Regular ed.), v 43(7), pp 493-504
Jul 2020
PMID: 32434664
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Tau, a microtubule-associated protein that modifies the dynamic properties and organization of microtubules in neurons and affects axonal transport, shows remarkable heterogeneity, with multiple isoforms (45–65 kDa) generated by alternative splicing. A high-molecular-weight (HMW) isoform (110 kDa) that contains an additional large exon termed 4a was discovered more than 25 years ago. This isoform, called Big tau, is expressed mainly in the adult peripheral nervous system (PNS), but also in adult neurons of the central nervous system (CNS) that extend processes into the periphery. Surprisingly little has been learned about Big tau since its initial characterization, leaving a significant gap in knowledge about how the dramatic switch to Big tau affects the properties of neurons in the context of development, disease, or injury. Here we review what was learned about the structure and distribution of Big tau in those earlier studies, and add contemporary insights to resurrect interest in the mysteries of Big tau and thereby set a path for future studies.
Tau is a highly studied protein, but most work on tau ignores the existence of Big tau, an isoform (discovered over 25 years ago) with a large additional exon (termed 4a) that doubles the size of the protein.The switch from low-molecular-weight (LMW) isoforms of tau to Big tau occurs in most PNS neurons as they mature into adulthood, with the selective expression of Big tau in these neurons as well as certain neuronal populations of the CNS (those extending axons into the periphery) remaining a puzzle.CNS neurons with axons projecting to the periphery also express Big tau as they mature into adulthood, including spinal motor neurons, retinal ganglion cells, and many cranial nerve neurons.The region of Big tau corresponding to exon 4a has almost no homology to known proteins and almost no putative phosphorylation sites, suggesting that it arose evolutionarily from an intron of another protein.Functional distinctions between Big tau and LMW isoforms may involve differences in their impact on axonal transport and microtubule spacing, as well as the lower propensity of Big tau to form toxic aggregates and fibrils.
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Details
- Title
- Resurrecting the Mysteries of Big Tau
- Creators
- Itzhak Fischer - Drexel UniversityPeter W. Baas - Drexel University
- Publication Details
- Trends in neurosciences (Regular ed.), v 43(7), pp 493-504
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000544550100007
- Scopus ID
- 2-s2.0-85084744388
- Other Identifier
- 991019168052204721
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- Web of Science research areas
- Neurosciences