Biology subjects

Saurin, A. J.

Publications and source records attributed to Saurin, A. J..

4 recordsLinked to original sources

bioRxiv2026

Intrinsically disordered regions influence protein motif usage in Drosophila Ubx and AbdA Hox proteins

Hox proteins are evolutionary conserved transcription factors guiding morphogenesis in all bilaterian animals. Conservation mainly concerns the homeodomain (HD), a helix-turn-helix DNA binding motif and flanking sequences close by. Besides, sequences are poorly conserved and disordered. Here we investigate how poorly conserved Intrinsically Disordered Regions (IDRs) influence Hox protein activity, focusing on a closely related Drosophila Hox pair and using a wide range of in vivo function. Studying Drosophila Ultrabithorax (Ubx) and AbdominalA (AbdA) proteins, we find that conserved protein motifs close to the HD are differently used in Ubx and AbdA. Coarse-grained molecular dynamics simulations identify a large set of intra-molecular interactions, notably involving poorly conserved disordered regions upstream and downstream the HD. Swapping these regions in Ubx and AbdA alters protein functions and switches motif dependency in some biological situations. This suggests that IDRs, predicted to mediate large and dynamic sets of intramolecular interactions, influence protein motif usage in a context dependent manner.

developmental biology↗

bioRxiv2023

Gut microbiota promotes pain chronicity in Myosin1A deficient male mice

Over the past decade, the gut microbiota has emerged as an important regulator of nervous systems health and disease states1. Yet, its contribution to the pathogenesis of chronic somatic pain remains poorly documented. Chronic pain is a heavily debilitating disease affecting more than 1.5 billion people worldwide that can manifest through a long-lasting hypersensitivity to mechanical and/or thermal stimulations2,3. Maladaptive responses of dorsal root ganglia (DRG) neurons and spinal cord (SC) interneurons to tissue injuries and also of non-neuronal cells including DRG macrophages and SC microglia are acknowledged as important drivers of sensory symptoms underlying chronic pain4,3,5-7. Recent evidence shows that signals from gut microbiota are required for the initiation of injury-induced sensory hypersensitivity, via the ability to interact with the immune system8-11. However, whether and how gut microbiota promotes pain chronicity remains unknown. Here, we report that male mice lacking Myosin1a (KO)12 raised under single genotype housing conditions (KO-SGH) are predisposed to develop chronic injury-induced mechanical pain. We demonstrate that this predisposition is caused by their dysbiotic gut microbiota, which sustains the immune response in the DRG following neuropathic injury. Parental antibiotic treatment modifies gut microbiota composition and completely rescues the injury-induced chronic pain and associated DRG inflammatory response in male KO-SGH offspring. Together, our data establish a causal relationship between a dysbiotic gut microbiota and the predisposition to injury-induced chronic pain.

neuroscience↗

bioRxiv2021

Haploinsufficiency of the mouse Tshz3 gene leads to kidney dysfunction

Renal tract defects and autism spectrum disorder (ASD) deficits represent the phenotypic core of the 19q12 deletion syndrome caused by the loss of one copy of the TSHZ3 gene. While a proportion of Tshz3 heterozygous (Tshz3+/lacZ) mice display ureteral defects, no kidney defects have been reported in these mice. The purpose of this study was to characterize the expression of Tshz3 in adult kidney as well as the renal physiological consequences of embryonic haploinsufficiency of Tshz3 by analyzing the morphology and function of Tshz3 heterozygous adult kidney. Here, we described Tshz3 expression in the smooth muscle and stromal cells lining the renal pelvis, the papilla and glomerular endothelial cells (GEnCs) of the adult kidney. Histological analysis showed that Tshz3+/lacZ adult kidney had an average of 29% fewer glomeruli than wild type kidney. Transmission electron microscopy (TEM) of Tshz3+/lacZ glomeruli revealed ultrastructural defects. Compared to wild type, Tshz3+/lacZ mice showed no difference in their urine parameters but lower blood urea, phosphates, magnesium and potassium at 2 months of age. At the molecular level, transcriptome analysis identified differentially expressed genes related to inflammatory processes in Tshz3+/lacZ compare to wild type (WT; control) adult kidneys. Lastly, analysis of the urinary peptidome revealed 33 peptides associated with Tshz3+/lacZ adult mice. These results provide the first evidence that in the mouse Tshz3 haploinsufficiency leads to cellular, molecular and functional abnormalities in the adult mouse kidney.

genetics↗

bioRxiv2019

Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation

Autophagy is an essential cellular process that maintains homeostasis by recycling damaged organelles and nutrients during development and cellular stress. ZKSCAN3 is the sole identified master transcriptional repressor of autophagy in humans. How ZKSCAN3 achieves autophagy repression at the mechanistic or organismal level however still remains to be elucidated. Here, we demonstrate that vertebrate ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy repression. Expression of ZKSCAN3 in Drosophila prevents premature autophagy onset due to loss of M1BP function and conversely, M1BP expression in human cells can prevent starvation-induced autophagy due to loss of nuclear ZKSCAN3 function. In Drosophila ZKSCAN3 binds genome-wide to sequences targeted by M1BP and transcriptionally regulates the majority of M1BP-controlled genes. These data allow the potential for transitioning the mechanisms, gene targets and plethora metabolic processes controlled by M1BP onto ZKSCAN3 and opens up Drosophila as a tool in studying the function of ZKSCAN3 in autophagy and tumourigenesis.

cell biology↗