Role of tau phosphorylation in formation of tau envelopes
Tau is an intrinsically-disordered microtubule-associated protein important for axonal development and a critical regulator of microtubule functions in axons. Tau activity is controlled by phosphorylation and its deregulation resulting in tau hyperphosphorylation and aggregation has been linked to m...
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Univerzita Karlova, Přírodovědecká fakulta
2023
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ftunivpraha:oai:https://dspace.cuni.cz:20.500.11956/181446 2023-08-20T04:10:07+02:00 Role of tau phosphorylation in formation of tau envelopes Role tau fosforylace ve formaci tau obálek Karhanová, Adéla Lánský, Zdeněk Štěpánek, Luděk 2023 application/pdf https://hdl.handle.net/20.500.11956/181446 English en_US eng Univerzita Karlova, Přírodovědecká fakulta http://hdl.handle.net/20.500.11956/181446 240709 tau tau phosphorylation tau envelopes tau islands tau patches microtubules microtubule-associated protein MAPs molecular motors kinesin severing enzymes katanin neurodegeneration Alzheimer's disease tau forforylace tau obálky tau ostrovy tau záplaty mikrotubuly proteiny asociované s mikrotubuly molekulární motory enzymy rozdělující mikrotubuly neurodegenerace Alzheimerova choroba diplomová práce 2023 ftunivpraha https://doi.org/20.500.11956/181446 2023-08-01T20:03:16Z Tau is an intrinsically-disordered microtubule-associated protein important for axonal development and a critical regulator of microtubule functions in axons. Tau activity is controlled by phosphorylation and its deregulation resulting in tau hyperphosphorylation and aggregation has been linked to multiple neurodegenerative disorders, collectively termed tauopathies. On microtubules, tau molecules segregate into two kinetically distinct phases, consisting of either independently diffusing molecules or interacting molecules that form cohesive "envelopes" around microtubules. Tau envelopes regulate the action of other microtubule-associated proteins, such as the motility of molecular motors, and protect microtubules against degradation by microtubule-severing enzymes. How the formation, dynamics, and function of tau envelopes are regulated, however, is unknown. Here we show that tau phosphorylation impedes the formation and functioning of protective tau envelopes. Using a combination of reconstitution experiments and live cell imaging, we show that phosphorylated tau incorporates into tau envelopes and that it slows down the envelope growth. Importantly, we demonstrate that phosphorylated tau also destabilizes already existing envelopes leading to their disassembly. Together, our results demonstrate. Tau je nestrukturovaný protein asociovaný s mikrotubuly důležitý pro vývoj axonů a kritický regulátor funkcí mikrotubulů v axonech. Aktivita Tau je řízena fosforylací a její deregulace vedoucí k hyperfosforylaci a agregaci tau je spojena s četnými neurodegenerativními poruchami, souhrnně nazývanými tauopatie. Na mikrotubulech se molekuly tau segregují do dvou kineticky odlišných fází, které se skládají buď z nezávisle difundujících molekul, nebo interagujících molekul, které tvoří soudržné "obálky" kolem mikrotubulů. Tau obálky regulují působení jiných proteinů asociaovaných s mikrotubuly, jako je pohyb molekulárních motorů, a chrání mikrotubuly před degradací enzymy rozdělujícími mikrotubuly. Jak je však formace, ... Thesis Tau Islands Charles University CU Digital repository Tau Islands ENVELOPE(-62.917,-62.917,-64.300,-64.300) |
institution |
Open Polar |
collection |
Charles University CU Digital repository |
op_collection_id |
ftunivpraha |
language |
English |
topic |
tau tau phosphorylation tau envelopes tau islands tau patches microtubules microtubule-associated protein MAPs molecular motors kinesin severing enzymes katanin neurodegeneration Alzheimer's disease tau forforylace tau obálky tau ostrovy tau záplaty mikrotubuly proteiny asociované s mikrotubuly molekulární motory enzymy rozdělující mikrotubuly neurodegenerace Alzheimerova choroba |
spellingShingle |
tau tau phosphorylation tau envelopes tau islands tau patches microtubules microtubule-associated protein MAPs molecular motors kinesin severing enzymes katanin neurodegeneration Alzheimer's disease tau forforylace tau obálky tau ostrovy tau záplaty mikrotubuly proteiny asociované s mikrotubuly molekulární motory enzymy rozdělující mikrotubuly neurodegenerace Alzheimerova choroba Karhanová, Adéla Role of tau phosphorylation in formation of tau envelopes |
topic_facet |
tau tau phosphorylation tau envelopes tau islands tau patches microtubules microtubule-associated protein MAPs molecular motors kinesin severing enzymes katanin neurodegeneration Alzheimer's disease tau forforylace tau obálky tau ostrovy tau záplaty mikrotubuly proteiny asociované s mikrotubuly molekulární motory enzymy rozdělující mikrotubuly neurodegenerace Alzheimerova choroba |
description |
Tau is an intrinsically-disordered microtubule-associated protein important for axonal development and a critical regulator of microtubule functions in axons. Tau activity is controlled by phosphorylation and its deregulation resulting in tau hyperphosphorylation and aggregation has been linked to multiple neurodegenerative disorders, collectively termed tauopathies. On microtubules, tau molecules segregate into two kinetically distinct phases, consisting of either independently diffusing molecules or interacting molecules that form cohesive "envelopes" around microtubules. Tau envelopes regulate the action of other microtubule-associated proteins, such as the motility of molecular motors, and protect microtubules against degradation by microtubule-severing enzymes. How the formation, dynamics, and function of tau envelopes are regulated, however, is unknown. Here we show that tau phosphorylation impedes the formation and functioning of protective tau envelopes. Using a combination of reconstitution experiments and live cell imaging, we show that phosphorylated tau incorporates into tau envelopes and that it slows down the envelope growth. Importantly, we demonstrate that phosphorylated tau also destabilizes already existing envelopes leading to their disassembly. Together, our results demonstrate. Tau je nestrukturovaný protein asociovaný s mikrotubuly důležitý pro vývoj axonů a kritický regulátor funkcí mikrotubulů v axonech. Aktivita Tau je řízena fosforylací a její deregulace vedoucí k hyperfosforylaci a agregaci tau je spojena s četnými neurodegenerativními poruchami, souhrnně nazývanými tauopatie. Na mikrotubulech se molekuly tau segregují do dvou kineticky odlišných fází, které se skládají buď z nezávisle difundujících molekul, nebo interagujících molekul, které tvoří soudržné "obálky" kolem mikrotubulů. Tau obálky regulují působení jiných proteinů asociaovaných s mikrotubuly, jako je pohyb molekulárních motorů, a chrání mikrotubuly před degradací enzymy rozdělujícími mikrotubuly. Jak je však formace, ... |
author2 |
Lánský, Zdeněk Štěpánek, Luděk |
format |
Thesis |
author |
Karhanová, Adéla |
author_facet |
Karhanová, Adéla |
author_sort |
Karhanová, Adéla |
title |
Role of tau phosphorylation in formation of tau envelopes |
title_short |
Role of tau phosphorylation in formation of tau envelopes |
title_full |
Role of tau phosphorylation in formation of tau envelopes |
title_fullStr |
Role of tau phosphorylation in formation of tau envelopes |
title_full_unstemmed |
Role of tau phosphorylation in formation of tau envelopes |
title_sort |
role of tau phosphorylation in formation of tau envelopes |
publisher |
Univerzita Karlova, Přírodovědecká fakulta |
publishDate |
2023 |
url |
https://hdl.handle.net/20.500.11956/181446 |
long_lat |
ENVELOPE(-62.917,-62.917,-64.300,-64.300) |
geographic |
Tau Islands |
geographic_facet |
Tau Islands |
genre |
Tau Islands |
genre_facet |
Tau Islands |
op_relation |
http://hdl.handle.net/20.500.11956/181446 240709 |
op_doi |
https://doi.org/20.500.11956/181446 |
_version_ |
1774724070242254848 |