Biology subjects

Horton, E.

Publications and source records attributed to Horton, E..

4 recordsLinked to original sources

bioRxiv2025

Ancient Truncated FtsZ Paralogs Likely Tune Cell Division in Hyphomicrobiales

Bacterial cell division is a well conserved, tightly regulated process that allows the separation of two viable daughter cells. In most bacteria, the proteins that drive division, termed the divisome, are recruited to mid-cell by FtsZ after it polymerizes to form the Z- ring. Interestingly, FtsZ has undergone several independent duplication events across the bacterial kingdom. We identified FtsZ GTPase protein sequences across alphaproteobacterial genomes, from representative genera for each family, and observed numerous ftsZ duplications in the order Hyphomicrobiales. Hidden Markov Modeling (HMM) supported the maintenance of two distinct lineages of FtsZ GTPase duplications among three families. The Nitrobacteraceae duplication, occurring in only the genus Bradyrhizobium, exhibits a different substitution pattern from that shared by the Phyllobacteraceae and Rhizobiaceae families. Within the Rhizobiaceae lineage, Agrobacterium tumefaciens contains three paralogs of FtsZ including the essential FtsZAT, and paralogs FtsZ1, and FtsZ3. In A. tumefaciens, we show that FtsZ1, but not FtsZ3, inhibits cell division when overexpressed. A hyperactive allele of ftsW partially protected against overexpression of ftsZ1 suggesting that FtsZ1 may inhibit proper regulation of septal peptidoglycan biosynthesis during cell division. Overall, these observations suggest that maintenance of FtsZ paralogs in some bacteria which may fine tune the division process. Article SummaryGene duplication drives evolutionary innovation by providing raw genetic material and allowing microbes to acquire novel functions. Here, we explore the duplication of a gene encoding the essential cell division protein FtsZ in the Hyphomicrobiales and find that the duplication is primarily conserved in genera that interact with plant hosts. In A. tumefaciens FtsZ1 is not essential for cell division; however, overexpression of FtsZ1 inhibited cell division suggesting it may have a regulatory role during this essential process. This observation highlights the key role for gene duplication in the modulation of complex processes in bacteria.

microbiology↗

bioRxiv2024

UBR4 regulates a MetAP2-dependent Arg/N-degron pathway

The open reading frame does more than merely encode a linear peptide sequence; it is a reservoir of regulatory information. Here, as part of investigations into how the N-terminal amino acids regulate translation, we serendipitously uncovered a new N-degron that revealed an additional layer of regulation in these pathways. Using reporter assays, we discovered that peptides bearing position 3 arginine or lysine residues at the N-terminus were rapidly degraded in mammalian cells. We found this pathway requires MetAP2, which co-translationally cleaves the N-terminal methionine preceding second position threonine and valines to initiate protein decay. We used CRISPR-Cas9 to knockout key N-recognins and found that these N-degrons are exclusively targeted by the E3 ligase UBR4, but not by UBR1 or UBR2. Together, our results characterize a new N-degron pathway that reveals a unique role for MetAP2 and UBR4 in mediating protein decay. SIGNIFICANCEThe Arg/N-degron pathway targets position 1 or 2 N-terminal Lys and Arg residues via UBR Box E3 ligases to trigger protein decay. Here we show that UBR4 can specifically recognize position 3 Lys and Arg N-termini upon methionine removal by the methionine amino peptidase MetAP2. Accordingly, proteins that bear N-terminal residues that are processed by MetAP1 are unaffected by the loss or inhibition of MetAP2. Using a combination of reporter assays, and bioinformatic approaches were identified endogenous proteins whose N-termini are recognized by this MetAP2-dependent Arg/N-degron pathway. Thus, our results expand the number of Arg/N-degron substrates and describe a new mechanism through which they are targeted.

molecular biology↗

bioRxiv2023

The Neonatal Gyrencephalic Cortex Maintains Regionally Distinct Streams of Neuroblasts

Neurodevelopmental mechanisms have evolved to support the formation of diverse brain structures, such as in humans, during the perinatal period. Here, we demonstrate that neonatal gyrencephalic brains harbor an expanded subventricular zone, termed the Arc, defined by tiered arrangement of doublecortin (DCX)-expressing neuroblasts and vascular enrichment at the ventricular wall. The Arc is the origin of dorsal and ventral populations of migratory neuroblasts that target multiple regions involved in higher cognitive functions. Arc-derived migratory streams, primarily from the caudal ganglionic eminence, are composed of diverse neuronal subtypes with distinct spatial and migratory-receptor profiles. Our findings indicate the Arc is a structure present in phylogenetically divergent species that supports the expansion of postnatal neuronal migration, contributing to a protracted formation of cortical circuits in gyrencephalic brains. One-Sentence SummaryThe ventricular cytoarchitecture of gyrencephalic brains supports an ongoing supply of migratory neurons to the neonatal cortex.

neuroscience↗

bioRxiv2022

Skin-resident immune cells engulf axonal debris in adult epidermis

Somatosensory neurons extend enormous peripheral axons to the skin, where they detect diverse environmental stimuli. Somatosensory peripheral axons are easily damaged due to their small caliber and superficial location. Axonal damage results in Wallerian degeneration, creating vast quantities of cellular debris that phagocytes must remove to maintain organ homeostasis. The cellular mechanisms that ensure efficient clearance of axon debris from stratified adult skin are unknown. Here, we establish zebrafish scales as a tractable model to study axon degeneration in the adult epidermis. Using this system, we demonstrate that skin-resident immune cells known as Langerhans cells engulf the majority of axon debris. In contrast to immature skin, adult keratinocytes do not significantly contribute to debris removal, even in animals lacking Langerhans cells. Our study establishes a powerful new model for studying Wallerian degeneration and identifies a new function for Langerhans cells in maintenance of adult skin homeostasis following injury. These findings have important implications for pathologies that trigger somatosensory axon degeneration.

cell biology↗