CLIC5A binds to and stabilizes the open and active conformation of ezrin
Bibliographic record
Abstract
Ezrin, radixin and moesin regulate assembly of actin-based structures, link membrane-spanning proteins to cortical actin and are part of cell signalling hubs. The CLIC5A protein is very abundant in radixin-dependent inner ear hair cell stereocilia and in ezrin-dependent kidney glomerular podocyte foot processes and is essential for the structural integrity of these actin-based cellular projections. The functional relationship between ERM proteins and CLIC5A is incompletely understood and whether CLIC5A functions as a chloride channel is controversial. We determined whether CLIC5A is membrane-spanning protein and sought direct CLIC5A binding partners. While CLIC5A localized predominantly to the dorsal plasma membrane domain, we found CLIC5A to be a soluble, intracellular protein, without characteristics expected of a membrane-spanning channel. In the yeast-two-hybrid assay CLIC5A interacted directly with the C-terminal domains of ezrin, radixin and moesin with a hierarchy of ezrin > radixin=moesin. The last 16 amino acids of ezrin were essential but not sufficient for CLIC5A binding, and phosphorylation of ezrin at T567 enhanced the interaction. The affinity of purified CLIC5A for a phosphomimetic ezrin 482-586 (T567E) C-terminal fragment was in the 30 μM range. Silencing of ezrin, radixin and moesin dislodged CLIC5A from the peripheral location, and the CLIC5A-ezrin interaction augmented Rho-GDI sequestration by ezrin and Rac1 activity. Thus, CLIC5A functions as a direct binding partner of ezrin, stabilizing its open/active conformation and resulting in localized small GTPase activation.
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) | 0.002 | 0.001 |
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".