The cytoplasmic domains of the CNNM family of transmembrane proteins modulate the ion channel-kinase TRPM7
Bibliographic record
Abstract
The ion channel and kinase TRPM7 contribute to a wide range of physiological and pathological processes, yet how it is controlled by signaling pathways remains poorly understood. Members of the CNNM family of transmembrane proteins (CNNM1-4) have been shown to selectively bind and regulate the TRPM7 channel. CNNM-binding partners, including the PRL family of proteins (PRL1-3) and ARL15, also modulate TRPM7 channel function. However, the regulation of TRPM7's kinase activity in vivo remains unclear. CNNMs contain a DUF21 transmembrane domain, a CBS-pair domain, followed by a COOH-terminal CNBH domain. Here, we identified multiple interaction sites between TRPM7 and CNNMs. The CNNM transmembrane domain was sufficient to mediate assembly of the CNNM2-TRPM7 complex, while the CBS-pair and CNBH domains provided additional points of contact. Electrophysiological analysis revealed that the CBS-pair domain modulates TRPM7 channel activity. ARL15, a known suppressor of TRPM7 channel function, required the CNNM CBS-pair domain to inhibit channel activity. Additionally, the CNNM2 CNBH domain bound to the TRPM7 kinase domain and modestly enhanced its catalytic activity in vitro. Collectively, these findings demonstrate that the cytoplasmic domains of CNNMs play critical roles in regulating TRPM7 channel and kinase activities.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".