Author response: Palmitoylation of LIM Kinase-1 ensures spine-specific actin polymerization and morphological plasticity
Bibliographic record
Abstract
Neurons transmit information from one cell to the next by passing signals across junctions called synapses. For the neurons that receive these signals, these junctions are found on fine branch-like structures called dendrites that stick out of the cell. Dendrites themselves are decorated with smaller structures called dendritic spines, which typically receive information from one other neuron via a single synapse. Dendritic spines form in response to the signaling activity of the neuron, and problems with forming these spines have been linked to conditions such as autism and schizophrenia. Dendritic spines are created by the cell's cytoskeleton—a network of proteins that creates a constantly changing internal scaffold that shapes cells. One cytoskeleton protein called actin exists as thin filaments that can be extended or broken up by other proteins. It is not fully understood how actin is regulated in the dendritic spines. However, some researchers thought that the proteins that control the formation of the actin filaments would need to be localized to the dendritic spines to ensure that the spines form correctly. Some proteins can be made to localize to cell membranes by attaching a molecule called palmitic acid to them. Previous research has suggested that this ‘palmitoylation’ process is particularly important in neurons. Through a combination of experimental techniques, George et al. now show that palmitoylation is required to localize a protein called LIMK1, which regulates the construction of actin filaments, to the tips of dendritic spines. Further experiments showed that blocking the palmitoylation of LIMK1 alters how actin filaments form, makes spines unstable and causes synapses to be lost. George et al. also discovered that palmitoylation is necessary for LIMK1 to be activated by another protein that is found at dendritic spine membranes. This ‘dual-control’ mechanism makes it possible to precisely control where actin filaments form within dendritic spines. In addition to LIMK1, several other enzymes are also modified by palmitoylation. It will therefore be interesting to determine whether this dual control mechanism is broadly used by neurons to precisely regulate the structure and function of individual spines and synapses.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.154 | 0.063 |
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".