Brain receptors reveal protein partners on both sides of cell membranes

A light-activated method mapped nearby proteins around several receptors in living mouse brains and identified one receptor partnership in mice and humans.

Editorial illustration — not from the study.

The method, called transmembrane PhoxID, uses a light-sensitive molecule attached to the outside of a transmembrane receptor. Light produces singlet oxygen, a reactive form of oxygen that can cross the cell membrane, allowing nearby proteins on both sides to be labelled for identification.

The researchers used the method on GRID2, GABAAR and GRM1 receptors in living mouse brains. The labelled proteins included components of transsynaptic nanocolumns at parallel fibre–Purkinje cell synapses, and the study identified a previously uncharacterized interaction between GABAAR and CAMKV in mouse and human brains.

Protein partners near brain receptors

Transmembrane PhoxID simultaneously labelled proteins near the extracellular and intracellular sides of targeted transmembrane receptors. Applied to GRID2, GABAAR and GRM1 in living mouse brains, it identified receptor-specific proteins close to the membrane. Network analysis showed that the GRID2 results included many proteins associated with transsynaptic nanocolumns at parallel fibre–Purkinje cell synapses. The researchers also identified a previously uncharacterized GABAAR–CAMKV interaction in mice and human brains. The method worked without adding a catalyst or enzyme to the intracellular part of the target receptor.

Why both sides matter

Transmembrane proteins coordinate signals and transport using protein partners on both sides of the cell membrane. Existing proximity-labelling approaches generally focus on one side because their reactive substances cannot readily cross the membrane. By providing a way to examine both sides around a receptor in its native brain environment, transmembrane PhoxID could help researchers study how receptor-associated protein networks are organized across cell–cell contacts.

Evidence and caveats

This was an experimental proof-of-concept study using proximity labelling, biochemical analysis and network analysis in living mouse brains, with the reported GABAAR–CAMKV finding also examined in human brain material. The researchers say the detailed chemical mechanism is not yet fully established, although their data indicate that major lipid oxidation or loss of membrane integrity does not explain the labelling. Designing receptor-specific light-sensitive probes can require time-consuming, case-by-case optimization and validation. The results demonstrate the approach for the receptors and brain settings tested; they do not establish that it will work identically for all transmembrane proteins or tissues.

Twenty years of no-till farming improved Central Valley soil structure and water holding

A 20-year comparison in California’s Central Valley found that reduced tillage with cover crops produced more stable soil aggregates, greater water retention and different forms of carbon protection than standard tillage without cover crops. The conservation system also retained room for additional carbon storage, although the study measured potential rather than future gains.

1 hour ago

Biology

Human brain organoids classified Braille letters with up to 83% accuracy

Human forebrain organoids classified artificial tactile Braille signals after a sensor converted the touch data into electrical stimulation. Accuracy averaged 61% with one organoid and rose to 83% when responses from three organoids were combined.

2 hours ago·2 views

Biology

A peptide reduced persistent traumatic memories in mice

A study in mice found that a peptide targeting the memory-related protein CPEB3 reduced the persistence of traumatic memories and anhedonia, a loss of pleasure. The findings are an early genetic preclinical test of a possible approach for PTSD, not evidence of a treatment in people.

8 hours ago·5 views