Biology subjects

Gumy, L. F.

Publications and source records attributed to Gumy, L. F..

3 recordsLinked to original sources

bioRxiv2026

MAP1A cleavage regulates TRIM46 transport to the axon in mature neurons

Polarised cargo transport is fundamental to neuronal function, ensuring the proper distribution of proteins and organelles between the cell body and axon. This process is tightly regulated at the proximal axon, where the enrichment of specific proteins organises the local cytoskeleton and directs intracellular trafficking. Although several microtubule-associated proteins (MAPs) have been implicated in axonal cargo transport during neuronal development, how protein localisation is maintained in mature neurons remains poorly understood. Here, we identify a previously unrecognised role for MAP1A in transporting TRIM46, a key organiser of the axonal microtubule cytoskeleton, to the axon of mature neurons, where it supports axon morphology. We show that MAP1A is enriched in the proximal axon and that its cleavage by Calpain-10 into heavy and light chains is required for TRIM46 localisation to this compartment. Mechanistically, the MAP1A light chain interacts with both TRIM46 and the tail domains of KIF3 motors, defining a transport complex that facilitates TRIM46 delivery to the proximal axon. Together, these findings establish proteolytic processing of a microtubule-associated protein as a mechanism regulating axonal protein distribution and neuronal polarity in mature neurons.

neuroscience↗

bioRxiv2022

Type III CRISPR-Cas provides resistance against nucleus-forming jumbo phages via abortive infection

Bacteria have diverse defences against phages. In response, jumbo phages evade multiple DNA-targeting defences by protecting their DNA inside a nucleus-like structure. We previously demonstrated that RNA-targeting type III CRISPR-Cas systems provide jumbo phage immunity by recognising viral mRNA exported from the nucleus for translation. Here, we demonstrate that recognition of phage mRNA by the type III system activates a cyclic triadenylate-dependent accessory nuclease, NucC. Although unable to access phage DNA in the nucleus, NucC degrades the bacterial chromosome, triggers cell death, and disrupts phage replication and maturation. Hence, type III-mediated jumbo phage immunity occurs via abortive infection, with suppression of the viral epidemic protecting the population. We further show that type III systems targeting jumbo phages have diverse accessory nucleases, including RNases that provide immunity. Our study demonstrates how type III CRISPR-Cas systems overcome the inaccessibility of jumbo phage DNA to provide robust immunity.

microbiology↗

bioRxiv2019

A nucleus-forming jumbophage evades CRISPR-Cas DNA targeting but is vulnerable to type III RNA-based immunity

CRISPR-Cas systems provide bacteria with adaptive immunity against bacteriophages1. However, DNA modification2,3, the production of anti-CRISPR proteins4,5 and potentially other strategies enable phages to evade CRISPR-Cas. Here we discovered a Serratia jumbophage that evaded type I CRISPR-Cas systems, but was sensitive to type III immunity. Jumbophage infection resulted in a nucleus-like structure enclosed by a proteinaceous phage shell - a phenomenon only reported recently for distantly related Pseudomonas phages6,7. All three native CRISPR-Cas complexes in Serratia - type I-E, I-F and III-A - were spatially excluded from the phage nucleus and phage DNA was not targeted. However, the type III-A system still arrested jumbophage infection by targeting phage RNA in the cytoplasm in a process requiring Cas7, Cas10 and an accessory nuclease. Type III, but not type I, systems frequently targeted nucleus-forming jumbophages that were identified in global viral sequence datasets. These findings explain why many bacteria harbour both RNA- and DNA-targeting CRISPR-Cas systems1,8. Together, our results indicate that jumbophage nucleus-like compartments serve as a barrier to DNA-targeting, but not RNA-targeting defences, and that this phenomenon is widespread amongst jumbophages.

microbiology↗