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Tafur, J.

Publications and source records attributed to Tafur, J..

3 recordsLinked to original sources

Spindle pole proteins confine chromosomes to ensure their expulsion during female meiosis

Animal oocytes undergo highly asymmetric divisions to expel excess copies of their genome into compact cells called polar bodies. This requires tight clustering and cortical positioning of meiotic chromosomes, yet the mechanism remains incompletely understood. Using C. elegans oocytes, we found that the meiotic spindle pole protein ZYG-9/ch-TOG delocalizes from microtubules to spread along the surface of chromosomes and prevent their dispersal in meiotic anaphase. This effect was more pronounced in the absence of the spindle, where ZYG-9 formed into a micron-scale droplet that enveloped all chromosomes. Purified ZYG-9 was sufficient to bind DNA and coat reconstituted chromatin. Mutations that perturb ZYG-9-DNA binding impaired chromosome packaging into polar bodies, resulting in oocytes carrying extra chromosomes and reduced fertility. We propose that liquid-like assemblies of spindle pole proteins are repurposed as surface-acting glue to tightly package meiotic chromosomes into polar bodies, thus ensuring oocytes have the correct genome copy number.

cell biology↗

TRIM37 recognizes a bipartite degron to ubiquitinate centrosome substrates

Dysregulation of the E3 ubiquitin ligase TRIM37 is associated with tumor formation and Mulibrey nanism, a recessive developmental syndrome. TRIM37 regulates steady-state levels of centrosome proteins and limits their ectopic assembly, but how it recognizes and ubiquitinates its substrates is poorly understood. We found that TRIM37 directly ubiquitinates the centrosome-forming protein Cep192 at 7 lysines clustered near its C-terminus. TRIM37 binds Cep192 at a C-terminal intrinsically disordered region followed by an ASH domain (IDR+ASH8). Mutation of the 7 lysines or the IDR+ASH8 domain increased Cep192 levels and stability in cells, indicating loss of TRIM37-based regulation. Fusing IDR+ASH8 to an unrelated protein (GFP-EB1) was sufficient to enable its degradation via TRIM37. Biochemical assays revealed that IDR+ASH8 is primarily monomeric and binds TRIM37 via two separate coiled-coil motifs with mid-nanomolar affinity. We propose that the IDR+ASH8 motif is a bipartite degron for TRIM37, enabling it to target centrosome proteins and adjust their levels.

cell biology↗

Brain-epigenome wide association study (BEWAS) on the effects of two emerging psychedelics: ketamine & MDMA

Psychedelic compounds such as ketamine and MDMA have shown therapeutic promise for mood and trauma-related disorders, yet their molecular mechanisms remain unclear. This study applied a Brain-Epigenome-Wide Association Study (BEWAS) to assess DNA methylation changes in brain-enriched genes following treatment. Pre- and post-treatment blood (ketamine, N = 20) and saliva (MDMA, N = 16) samples from clinical trial participants were analyzed. Ketamine altered methylation at 1,210 CpG sites; MDMA affected 2,074 CpG sites. Functional enrichment analyses revealed changes in genes involved in neuroplasticity, immune regulation, and mental processes. Overlapping effects were observed in genes such as PTPRN2 and SHANK2, suggesting shared epigenetic mechanisms in driving increased neuroplasticity. These findings highlight psychedelics capacity to induce coordinated, lasting molecular changes relevant to neuroimmune function and psychiatric health.

genomics↗