Biology subjects

MacLellan-Gibson, K.

Publications and source records attributed to MacLellan-Gibson, K..

3 recordsLinked to original sources

bioRxiv2025

Prex1 controls glucose homeostasis by limiting glucose uptake and mitochondrial metabolism in liver through GEF-independent regulation of Gpr21

We investigated the roles of Rac guanine-nucleotide factor (Rac-GEF) Prex1 in glucose homeostasis using Prex1-/- and catalytically-inactive Prex1GD mice. Prex1 maintains fasting blood glucose levels and insulin sensitivity through its Rac-GEF activity but limits glucose clearance independently of its catalytic activity, throughout ageing. Prex1-/-mice on high-fat diet are protected from developing diabetes. The increased glucose clearance in Prex1-/- mice stems from constitutively enhanced hepatic glucose uptake. Prex1 limits Glut2 surface levels, mitochondrial membrane potential and mitochondrial ATP production, and controls mitochondrial morphology in hepatocytes, independently of its catalytic activity. Prex1 limits GPCR trafficking through an adaptor function, and we identify here the inhibitory orphan GPCR Gpr21 as a Prex1 target. The Gpr21-mediated blockade of glucose uptake and mitochondrial ATP production in hepatocytes requires Prex1. We propose that Prex1 limits glucose clearance by maintaining Gpr21 at the hepatocyte surface, thus limiting hepatic glucose uptake and metabolism. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/648781v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@110e660org.highwire.dtl.DTLVardef@84c0c3org.highwire.dtl.DTLVardef@18b8319org.highwire.dtl.DTLVardef@4bfde0_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2024

3D nanoscale architecture of the respiratory epithelium reveals motile cilia-rootlets-mitochondria axis of communication

A major frontier in single cell biology is decoding how transcriptional states result in cellular-level architectural changes, ultimately driving function. A remarkable example of this cellular remodelling program is the differentiation of airway stem cells into the human respiratory multiciliated epithelium, a tissue barrier protecting against bacteria, viruses and particulate matter. Here, we present the first isotropic three-dimensional map of the airway epithelium at the nanometre scale unveiling the coordinated changes in cellular organisation, organelle topology and contacts, occurring during multiciliogenesis. This analysis led us to discover a cellular mechanism of communication whereby motile cilia relay mechanical information to mitochondria through striated cytoskeletal fibres, the rootlets, to promote effective ciliary motility and ATP generation. Altogether, this study integrates nanometre-scale structural, functional and dynamic insights to elucidate fundamental mechanisms responsible for airway defence.

cell biology↗

bioRxiv2019

Cryo-OrbiSIMS for 3D molecular imaging of a bacterial biofilm in its native state

We describe a method for label-free molecular imaging of biological materials, preserved in a native state, by using an OrbiSIMS instrument equipped with cryogenic sample handling and developing a high-pressure freezing protocol compatible with mass spectrometry. We studied the 3D distribution of quorum sensing signalling molecules, nucleobases and bacterial membrane molecules, in a mature Pseudomonas aeruginosa biofilm, with high spatial-resolution and high mass-resolution.

microbiology↗