Biology subjects

Bodzeta, A.

Publications and source records attributed to Bodzeta, A..

3 recordsLinked to original sources

bioRxiv2026

The unhindered lateral mobility of a rhomboid intramembrane protease enables synapse remodelling

Synapses must maintain their stable molecular organisation while retaining the capacity to remodel in response to changing demands. In order to flexibly change synaptic strength, the abundance of trans-synaptic adhesion complexes needs to be modulated, yet how this is achieved is poorly understood. Here, we identify the rhomboid protease RHBDL2 as a membrane-immersed regulator of adhesion complexes that enables mature synapses to adjust their composition both at steady-state and during their active restructuring. To do so, RHBDL2 possesses unrestrained diffusion properties that enable it to constitutively scan the neuronal surface and remove available adhesion molecules through irreversible cleavage of their transmembrane domains. Demonstrating its physiological importance, diffusion-dependent membrane surveillance by RHBDL2 is required for synapses to undergo remodelling during long term depression. Overall, we reveal a mechanism that cells use to preserve functional signalling complexes in membranes while selectively removing dispensable transmembrane proteins.

neuroscience↗

bioRxiv2026

Kinase-gated coincidence detection controls kinesin-driven lysosome transport

Kinesin motors drive long-range intracellular transport through coordinated cargo recognition and conformational autoregulation, yet the mechanisms that selectively control cargo engagement remain unclear. Here, we identify a phosphorylation-dependent gate on kinesin-1 activity mediated by the carboxy-terminal domain (CTD) of kinesin light chain 2 (KLC2). The KLC2 CTD is constitutively phosphorylated on multiple serine residues, suppressing membrane association via its amphipathic helix. We identify the NIMA-related kinase NEK10 as a KLC2-selective regulator of kinesin-1, restraining motor activation, cargo engagement, and lysosome transport; conversely, loss of NEK10 increases membrane association and, together with low-affinity adaptor interactions, promotes lysosome motility. These findings reveal a phosphorylation-regulated protein-lipid coincidence-detection mechanism - a kinesin-kinase code - that integrates adaptor binding with membrane cues to control kinesin-1-mediated transport and provide a mechanistic basis for understanding paralogue and isoform diversity in the kinesin-1 family.

cell biology↗

bioRxiv2020

Distinct mechanisms underlie the subsynaptic mobility of presynaptic metabotropic glutamate receptor types to tune receptor activation

Presynaptic metabotropic glutamate receptors (mGluRs) are essential for activity-dependent modulation of synaptic transmission. However, the mechanisms that control the subsynaptic dynamics of these receptors and their contribution to synaptic signaling are poorly understood. Here, using complementary super-resolution microscopy and single-molecule tracking techniques, we provide novel insights into the molecular mechanisms that control the nanoscale distribution and mobility of presynaptic mGluRs in hippocampal neurons. We demonstrate that the group II receptor mGluR2 localizes diffusely along the axon and boutons, and is highly mobile, while the group III receptor mGluR7 is stably anchored at the active zone, indicating that distinct mechanisms underlie the dynamic distribution of these receptor types. Surprisingly, using domain swapping experiments we found that intracellular interactions modulate surface diffusion of mGluR2, but not mGluR7. Instead, we found that immobilization of mGluR7 at the active zone relies on its extracellular domain. Importantly, receptor activation or increase in synaptic activity did not alter the surface mobility of presynaptic mGluRs. Finally, computational modeling of presynaptic mGluR activity revealed that the precise subsynaptic distribution of mGluRs controls their activation probability and thus directly impacts their ability to modulate neurotransmitter release. Altogether, this study demonstrates that distinct mechanisms control surface mobility of presynaptic mGluRs to differentially contribute to the regulation of glutamatergic synaptic transmission.

neuroscience↗