Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends
Summary: Plus-end tracking proteins (+TIPs) associate with the growing end of microtubules and mediate important cellular functions. The majority of +TIPs are directed to the plus-end through a family of end-binding proteins (EBs), which preferentially bind the stabilizing cap of GTP-tubulin present...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220309792 |
| _version_ | 1818726773371699200 |
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| author | Brian T. Castle Kristen M. McKibben Elizabeth Rhoades David J. Odde |
| author_facet | Brian T. Castle Kristen M. McKibben Elizabeth Rhoades David J. Odde |
| author_sort | Brian T. Castle |
| collection | DOAJ |
| description | Summary: Plus-end tracking proteins (+TIPs) associate with the growing end of microtubules and mediate important cellular functions. The majority of +TIPs are directed to the plus-end through a family of end-binding proteins (EBs), which preferentially bind the stabilizing cap of GTP-tubulin present during microtubule growth. One outstanding question is whether there may exist other microtubule-associated proteins (MAPs) that preferentially bind specific nucleotide states of tubulin. Here, we report that the neuronal MAP tau preferentially binds GDP-tubulin (KD = 0.26 μM) over GMPCPP-tubulin (KD = 1.1 μM) in vitro, as well as GTP-tubulin at the tips of growing microtubules, causing tau binding to lag behind the plus-end both in vitro and in live cells. Thus, tau is a microtubule tip avoiding protein, establishing the framework for a possible new class of tip avoiding MAPs. We speculate that disease-relevant tau mutations may exert their phenotype by their failure to properly recognize GDP-tubulin. |
| first_indexed | 2024-12-17T22:03:32Z |
| format | Article |
| id | doaj.art-b978b96f865c4bef8f3df7519e3db59c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-17T22:03:32Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b978b96f865c4bef8f3df7519e3db59c2022-12-21T21:30:54ZengElsevieriScience2589-00422020-12-012312101782Tau Avoids the GTP Cap at Growing Microtubule Plus-EndsBrian T. Castle0Kristen M. McKibben1Elizabeth Rhoades2David J. Odde3Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USABiochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USABiochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding authorSummary: Plus-end tracking proteins (+TIPs) associate with the growing end of microtubules and mediate important cellular functions. The majority of +TIPs are directed to the plus-end through a family of end-binding proteins (EBs), which preferentially bind the stabilizing cap of GTP-tubulin present during microtubule growth. One outstanding question is whether there may exist other microtubule-associated proteins (MAPs) that preferentially bind specific nucleotide states of tubulin. Here, we report that the neuronal MAP tau preferentially binds GDP-tubulin (KD = 0.26 μM) over GMPCPP-tubulin (KD = 1.1 μM) in vitro, as well as GTP-tubulin at the tips of growing microtubules, causing tau binding to lag behind the plus-end both in vitro and in live cells. Thus, tau is a microtubule tip avoiding protein, establishing the framework for a possible new class of tip avoiding MAPs. We speculate that disease-relevant tau mutations may exert their phenotype by their failure to properly recognize GDP-tubulin.http://www.sciencedirect.com/science/article/pii/S2589004220309792Optical ImagingMolecular Biology Experimental ApproachCellular Neuroscience |
| spellingShingle | Brian T. Castle Kristen M. McKibben Elizabeth Rhoades David J. Odde Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends iScience Optical Imaging Molecular Biology Experimental Approach Cellular Neuroscience |
| title | Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends |
| title_full | Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends |
| title_fullStr | Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends |
| title_full_unstemmed | Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends |
| title_short | Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends |
| title_sort | tau avoids the gtp cap at growing microtubule plus ends |
| topic | Optical Imaging Molecular Biology Experimental Approach Cellular Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220309792 |
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