Structure, amphipathy, and topology of the membrane-proximal helix 8 influence apelin receptor plasma membrane localization

Pandey, Akhilesh; LeBlanc, Danielle M.; Parmar, Hirendrasinh B.; Phạm, Trần Thanh Tâm; Sarker, Muzaddid; Xu, Liang; Duncan, Roy; Liu, Xiang-Qin; Rainey, Jan K.

doi:10.1016/j.bbamem.2019.183036

Cited by 4 publications

(1 citation statement)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In various GPCRs, H8 has been implicated in receptor homodimerization (Salahpour et al, 2004;Knepp et al, 2012;Parmar et al, 2017), ER exit (Salahpour et al, 2004;Parmar et al, 2017), surface expression (Feierler et al, 2011;Spomer et al, 2014;Pandey et al, 2019), as a site of G protein coupling (Delos Santos et al, 2006;Kaye et al, 2011;Kuramasu et al, 2011;Kawasaki et al, 2015;Markx et al, 2019), and in β-arrestin binding (Feierler et al, 2011;Kirchberg et al, 2011;Kang et al, 2015;Yang et al, 2019) and subsequent internalization (Faussner et al, 2005;Aratake et al, 2012). Specifically in CB1R, disruption of H8 helicity and hydrophobicity impairs CB1R trafficking, causing it to accumulate in the ER (Ahn et al, 2010).…”

Section: Helix 8 (H8)mentioning

confidence: 99%

Protein Interactors and Trafficking Pathways That Regulate the Cannabinoid Type 1 Receptor (CB1R)

Fletcher‐Jones

Hildick

Evans

et al. 2020

Front. Mol. Neurosci.

View full text Add to dashboard Cite

The endocannabinoid system (ECS) acts as a negative feedback mechanism to suppress synaptic transmission and plays a major role in a diverse range of brain functions including, for example, the regulation of mood, energy balance, and learning and memory. The function and dysfunction of the ECS are strongly implicated in multiple psychiatric, neurological, and neurodegenerative diseases. Cannabinoid type 1 receptor (CB1R) is the most abundant G protein-coupled receptor (GPCR) expressed in the brain and, as for any synaptic receptor, CB1R needs to be in the right place at the right time to respond appropriately to changing synaptic circumstances. While CB1R is found intracellularly throughout neurons, its surface expression is highly polarized to the axonal membrane, consistent with its functional expression at presynaptic sites. Surprisingly, despite the importance of CB1R, the interacting proteins and molecular mechanisms that regulate the highly polarized distribution and function of CB1R remain relatively poorly understood. Here we set out what is currently known about the trafficking pathways and protein interactions that underpin the surface expression and axonal polarity of CB1R, and highlight key questions that still need to be addressed.

show abstract