Biology subjects

Pakulska, V.

Publications and source records attributed to Pakulska, V..

4 recordsLinked to original sources

bioRxiv2026

VASH1 phosphorylation regulates tubulin detyrosination via CNP/PRKG1α signaling in DRG neurons.

Functional neuronal circuit formation requires precise regulation of axon growth and branching through dynamic cytoskeletal remodeling. Although microtubule detyrosination/re-tyrosination critically controls microtubule dynamics, how extracellular signals regulate this process remains unclear. Here, we identify a direct link between C-type natriuretic peptide, protein kinase cGMP-dependent 1 (CNP/cGMP/PRKG1) signaling and microtubule detyrosination in dorsal root ganglion (DRG) neurons. CNP stimulation induces growth cone enlargement, increases tyrosinated tubulin within growth cones, and reduces detyrosinated tubulin along axons, effects abolished by PRKG1 inhibition. Pharmacological inhibition or genetic deletion of the detyrosinating enzyme VASH1 phenocopies CNP-induced growth cone remodeling. In vitro kinase assays identify VASH1 as a direct PRKG1 substrate and reveal a specific C-terminal serine phosphorylation site (serine 337) that suppresses VASH1-SVBP microtubule association and detyrosination activity. Together, these findings establish VASH1-SVBP as a key downstream effector linking extracellular guidance signaling to microtubule remodeling during DRG neuronal development.

cell biology↗

bioRxiv2025

Local B cell maturation and mast cell regulation of choroid plexus function in early life.

Postnatal development is a critical period for the maturation of the nervous and immune systems. The choroid plexus (CP) within the brain ventricles guides brain development through the production of cerebrospinal fluid and responds to stimuli from its local immune microenvironment. Here, using single-cell sequencing, we chart the establishment of the immune niche within the CP from birth to adulthood. We demonstrate that the CP is an active site for the development of B cells from early pro-B cells to mature B cells. We also characterize a transient population of CP mast cells that is highly abundant in the perinatal period. Single activation of these cells shortly after birth led to activation of serotonin-dependent secretion from the CP epithelial cells and resulted in cognitive impairment later in life. Our findings highlight the crucial nature of the CP as a neuroimmune interface, where cellular crosstalk regulates key functions of CP activity, thereby guiding brain development.

immunology↗

bioRxiv2024

Diurnal regulation of Acyl-CoA synthetase 3 (ACSF3) underlies daily mitochondrial lysine-malonylation and hepatic metabolism

Circadian rhythms are fundamental to maintaining health and are implicated in various diseases. In the liver, daily rhythms are coordinated via the interplay between feeding rhythms and the molecular circadian clock, ensuring metabolic homeostasis. Disruption of feeding rhythms can lead to circadian misalignment, contributing to metabolic disorders, yet the underlying molecular mechanisms remain unclear. Recent evidence suggests that post-translational modifications play a key role in regulating circadian functional output. In this framework, mitochondria serve as a convergence point, integrating rhythms in metabolism, feeding rhythms and the circadian clock. In the present study, we used a multi-omics approach to investigate the role of the Acyl-CoA synthetase 3 (ACSF3) in driving lysine-malonylation and in regulating daily hepatic metabolism. We found that ACSF3 expression and its mediated impact on lysine-malonylation are rhythmic and largely governed by feeding rhythms. While hepatic ACSF3 knockdown did not alter diet-induced metabolic abnormalities, our results demonstrate that ACSF3 plays a role in the diurnal regulation of liver glycogen storage, de novo lipogenesis, and triglyceride synthesis.

physiology↗

bioRxiv2023

SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans

The SIN3 transcriptional coregulator influences gene expression through multiple interactions that include histone deacetylases (HDACs). Haploinsufficiency and mutations in SIN3 are the underlying cause of Witteveen-Kolk syndrome and related intellectual disability (ID)/autism syndromes, emphasizing its key role in development. However, little is known about the diversity of its interactions and functions in developmental processes. Here we show that loss of SIN-3, the single SIN3 homologue in Caenorhabditis elegans, results in maternal effect sterility associated with deregulation of the germline transcriptome, including desilencing of X-linked genes. We identify at least two distinct SIN3 complexes containing specific HDACs, and show that they differentially contribute to fertility. Single cell smFISH reveals that in sin-3 mutants, the X chromosome becomes re-expressed prematurely and in a stochastic manner in individual germ cells. Furthermore, we identify histone residues whose acetylation increases in the absence of SIN3. Together, this work provides a powerful framework for the in vivo study of SIN3 and associated proteins.

genetics↗