Phase separation modulates the functional amyloid assembly of human CPEB3

التفاصيل البيبلوغرافية
العنوان:	Phase separation modulates the functional amyloid assembly of human CPEB3
المؤلفون:	Ramírez de Mingo, Daniel, López-García, Paula, Vaquero, María Eugenia, Hervás, Rubén, Laurents, Douglas V., Carrión-Vázquez, Mariano
المساهمون:	Comunidad de Madrid, Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Carrión-Vázquez, Mariano
بيانات النشر:	Elsevier
سنة النشر:	2023
المجموعة:	Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council)
مصطلحات موضوعية:	Amyloid, CPEB3, Hydrogel, LLPS, Memory consolidation
الوصف:	17 pags., 7 figs. ; How functional amyloids are regulated to restrict their activity is poorly understood. The cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is an RNA-binding protein that adopts an amyloid state key for memory persistence. Its monomer represses the translation of synaptic target mRNAs while phase separated, whereas its aggregated state acts as a translational activator. Here, we have explored the sequence-driven molecular determinants behind the functional aggregation of human CPEB3 (hCPEB3). We found that the intrinsically disordered region (IDR) of hCPEB3 encodes both an amyloidogenic and a phase separation domain, separated by a poly-A-rich region. The hCPEB3 amyloid core is composed by a hydrophobic region instead of the Q-rich stretch found in the Drosophila orthologue. The hCPEB3 phase separation domain relies on hydrophobic interactions with ionic strength dependence, and its droplet ageing process leads to a liquid-to-solid transition with the formation of a non-fibril-based hydrogel surrounded by starburst droplets. Furthermore, we demonstrate the differential behavior of the protein depending on its environment. Under physiological-like conditions, hCPEB3 can establish additional electrostatic interactions with ions, increasing the stability of its liquid droplets and driving a condensation-based amyloid pathway. ; Thanks the financial support of the Community of Madrid for her industrial PhD grant (IND2020/BMD-17444). This work was supported by grants SAF2013-49179-C2-1-R and SAF2016-76678-C2-1-R and PID2020-117847RB-I00/AEI/10.13039/501100011033 to MC-V and SAF2016-76678-C2-2-R to DVL from the Spanish Ministry of Economy and Competitiveness and the Ministry of Science and Innovation. ; Peer reviewed
نوع الوثيقة:	article in journal/newspaper
اللغة:	English
تدمد:	0301-0082
Relation:	#PLACEHOLDER_PARENT_METADATA_VALUE#; IND2020/BMD-17444; info:eu-repo/grantAgreement/MINECO//SAF2013-49179-C2-1-R/ES/QBP1 COMO AGENTE PROFILACTIO EN TEPT: ESTUDIOS ESTRUCTURALES Y PRECLINICOS/; info:eu-repo/grantAgreement/MINECO//SAF2016-76678-C2-1-R; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117847RB-I00/ES/DESARROLLO DE NUEVOS INHIBIDORES PARA AMILOIDES FUNCIONALES Y PATOLOGICOS BASADOS EN EL PEPTIDO QBP1/; info:eu-repo/grantAgreement/MINECO//SAF2016-76678-C2-2-R; Progress in neurobiology; Publisher's version; https://doi.org/10.1016/j.pneurobio.2023.102540; Sí; Progress in Neurobiology 231: 102540 (2023); http://hdl.handle.net/10261/344486; http://dx.doi.org/10.13039/501100003329; http://dx.doi.org/10.13039/501100011033; http://dx.doi.org/10.13039/100012818; 2-s2.0-85176908629; https://api.elsevier.com/content/abstract/scopus_id/85176908629
DOI:	10.1016/j.pneurobio.2023.102540
DOI:	10.13039/501100003329
DOI:	10.13039/501100011033
DOI:	10.13039/100012818
الاتاحة:	http://hdl.handle.net/10261/344486 https://doi.org/10.1016/j.pneurobio.2023.102540 https://doi.org/10.13039/501100003329 https://doi.org/10.13039/501100011033 https://doi.org/10.13039/100012818 https://api.elsevier.com/content/abstract/scopus_id/85176908629
Rights:	open
رقم الانضمام:	edsbas.9BD7806
قاعدة البيانات:	BASE

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الوصف
تدمد:	03010082
DOI:	10.1016/j.pneurobio.2023.102540