Critical impact of different conserved endoplasmic retention mofits and dopamine receptor interacting proteins (DRIPs) on intracellular localization and trafficking of the D$_2$ dopamine receptor (D$_2$-R) isoforms

Blagotinšek Cokan, Kaja (author), Mavri, Maša (author), Rutland, Catrin S. (author), Glisic, Sanja (author), Sencanski, Milan (author), Vrecl, Milka (author), Kubale, Valentina (author)

The type 2 dopamine receptor D$_2$ (D$_2$-R), member of the G protein-coupled receptor (GPCR) superfamily, exists in two isoforms, short (D$_{2S}$-R) and long (D$_{2L}$-R). They differ by an additional 29 amino acids (AA) in the third cytoplasmic loop (ICL3) of the D$_{2L}$-R. These isoforms differ in their intracellular localization and trafficking functionality, as D$_{2L}$-R possesses a larger intracellular pool, mostly in the endoplasmic reticulum (ER). This review focuses on the evolutionarily conserved motifs in the ICL3 of the D$_2$-R and proteins interacting with the ICL3 of both isoforms, specifically with the 29 AA insert. These motifs might be involved in D$_2$-R exit from the ER and have an impact on cell-surface and intracellular localization and, therefore, also play a role in the function of dopamine receptor signaling, ligand binding and possible homo/heterodimerization. Our recent bioinformatic data on potential new interaction partners for the ICL3 of D$_2$-Rs are also presented. Both are highly relevant, and have clinical impacts on the pathophysiology of several diseases such as Parkinson’s disease, schizophrenia, Tourette’s syndrome, Huntington’s disease, manic depression, and others, as they are connected to a variety of essential motifs and differences in communication with interaction partners.

• Language: English
• Keywords: D$_2$ dopamine receptor, intracellular trafficking, endoplasmic reticulum, retention motifs, ICL3, interacting partners
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: VF - Veterinary Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 18 str.
• Numbering: Vol. 10, iss. 10, art. 1355
• PID: 20.500.12556/RUL-134373
• UDC: 577
• ISSN on article: 2218-273X
• DOI: 10.3390/biom10101355
• COBISS.SI-ID: 29478403
• Publication date in RUL: 12.01.2022

Record is a part of a journal

• Title: Biomolecules
• Shortened title: Biomolecules
• Publisher: MDPI
• ISSN: 2218-273X
• COBISS.SI-ID: 519952921

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.10.2020