Related Experiment Video
Updated: Aug 3, 2026
Control of Eating Behavior Using a Novel Feedback System
Published on: May 8, 2018
Attractin' more attention - new pieces in the obesity puzzle?
Giles S H Yeo1, Kenneth Siddle
1Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, UK.
Abstract:
Genetic, biochemical and pharmacological studies in humans and rodents have established that signalling through the G-protein-coupled melanocortin-4 receptor (MC4R) by pro-opiomelanocortin (POMC)-derived ligands plays a critical role in the central suppression of appetite. As a consequence, malfunction of this signalling system leads to the development of obesity. It has been shown previously that melanocortin signalling can be modulated by the type 1 transmembrane protein attractin, apparently acting as a co-receptor for the inhibitory ligand agouti. Work reported in this issue of Biochemical Journal (Haqq et al.) demonstrates that the cytosolic tail of an attractin-like protein (ALP) binds directly and specifically to the C-terminal region of MC4R, raising the possibility that proteins of the attractin family influence melanocortin receptor function through multiple mechanisms.
Insights
The attractin-like protein (ALP) directly binds to the melanocortin-4 receptor (MC4R), suggesting a new mechanism for controlling appetite and potentially obesity. This interaction highlights a novel pathway for therapeutic intervention.
Area of Science:
- Endocrinology and Metabolism
- Molecular Cell Biology
- Neuroscience
Background:
- Signaling via the G-protein-coupled melanocortin-4 receptor (MC4R) is crucial for central appetite suppression.
- Dysfunction in this MC4R pathway is linked to obesity development.
- Attractin, a type 1 transmembrane protein, was previously identified as a modulator of melanocortin signaling, potentially acting as a co-receptor.
Discussion:
- This study reveals that the cytosolic tail of an attractin-like protein (ALP) directly and specifically binds to the C-terminal region of MC4R.
- This interaction suggests a novel mechanism by which attractin family proteins can influence MC4R function.
- The findings expand our understanding beyond ALP's potential role as a co-receptor for inhibitory ligands.
Key Insights:
- Direct binding of ALP's cytosolic tail to MC4R's C-terminus.
- Identification of a new molecular interaction in appetite regulation.
- Evidence for multiple mechanisms of attractin family influence on melanocortin receptor function.
Outlook:
- Further investigation into the functional consequences of the ALP-MC4R interaction.
- Exploring the therapeutic potential of targeting this interaction for obesity treatment.
- Elucidating the precise role of attractin family proteins in central appetite control.
