Biology subjects

Hajdu, R.

Publications and source records attributed to Hajdu, R..

4 recordsLinked to original sources

bioRxiv2025

Evolutionary repurposing of a DNA segregation machinery into a cytoskeletal system controlling cyanobacterial cell shape

Bacteria, like eukaryotes, use conserved cytoskeletal systems for intracellular organization. The plasmid-encoded ParMRC system forms actin-like filaments that segregate low-copy plasmids. In multicellular cyanobacteria like Anabaena sp., we found that a chromosomally-encoded ParMR has evolved into a novel cytoskeleton-termed CorMR-with a function in cell shape control rather than DNA segregation. Using live-cell imaging, in vitro reconstitution and Cryo-EM, we demonstrate that CorM forms dynamically unstable, antiparallel double-stranded filaments, which are recruited to the membrane by CorR via an amphipathic helix conserved in multicellular cyanobacteria. CorMR filaments are regulated by MinC, which excludes them from the poles and division plane. Comparative genomics reveal that the repurposing of ParMR and Min systems co-evolved with cyanobacterial multicellularity, highlighting the evolutionary plasticity of cytoskeletal systems in bacteria.

microbiology↗

bioRxiv2025

The aPBP-type cell wall synthase PBP1b plays a specialized role in fortifying the Escherichia coli division site against osmotic rupture

A multi-protein system called the divisome promotes bacterial division. This apparatus synthesizes the peptidoglycan (PG) cell wall layer that forms the daughter cell poles and protects them from osmotic lysis. In the model Gram-negative bacterium Escherichia coli, PG synthases called class A penicillin-binding proteins (aPBPs) have been proposed to play crucial roles in division. However, there is limited experimental support for aPBPs playing a specialized role in division that is distinct from their general function in the expansion and fortification of the PG matrix. Here, we present in situ cryogenic electron tomography data indicating that the aPBP-type enzyme PBP1b is required to produce a wedge-like density of PG at the division site. Furthermore, atomic force and live cell microscopy showed that loss of this structure weakens the division site and renders it susceptible to lysis. Surprisingly, we found that the lipoprotein activator LpoB needed to promote the general function of PBP1b was not required for normal division site architecture or its integrity. Additionally, we show that of the two PBP1b isoforms produced in cells, it is the one with an extended cytoplasmic N-terminus that functions in division, likely via recruitment by the FtsA component of the divisome. Altogether, our results demonstrate that PBP1b plays a specialized, LpoB-independent role in E. coli cell division involving the biogenesis of a PG structure that prevents osmotic rupture. The conservation of aPBPs with extended cytoplasmic N-termini suggests that other Gram-negative bacteria may use similar mechanisms to reinforce their division site.

microbiology↗

bioRxiv2023

Identification of a link between splicing and endoplasmic reticulum proteostasis

The role of general splicing in endoplasmic reticulum (ER)-proteostasis remains poorly understood. Here, we identify SNRPB, a component of the spliceosome, as a novel regulator of export from the ER. Mechanistically, SNRPB regulates the splicing of components of the ER export machinery, including Sec16A, a regulator of ER exit sites. Loss of function of SNRPB is causally linked to cerebro-costo-mandibular syndrome (CCMS), a genetic disease characterized by bone defects. We show that heterozygous deletion of SNRPB in mice resulted in intracellular accumulation of type-1 collagen as well as bone defects reminiscent of CCMS. Silencing SNRPB inhibited osteogenesis in vitro, which could be rescued by overexpression of Sec16A. This indicates that the role of SNRPB in osteogenesis is linked to its effects on ER export. Finally, we show that SNRPB is a target for the unfolded protein response (UPR), which supports a mechanistic link between the spliceosome and ER-proteostasis. Our work highlights SNRPB as a novel node in the proteostasis network, shedding light on CCMS pathophysiology.

cell biology↗

bioRxiv2018

Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates, and humans

Targeting genes to specific neuronal or glial cell types is valuable both for understanding and for repairing brain circuits. Adeno-associated viral vectors (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is a challenge. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that ~11% of these AAVs specifically target expression to neuronal and glial cell types in the mouse retina, mouse brain, non-human primate retina in vivo, and in the human retina in vitro. We demonstrate applications for recording, stimulation, and molecular characterization, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast, and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

neuroscience↗