Biology subjects

do Rego Barros Fernandes Lima, M. A.

Publications and source records attributed to do Rego Barros Fernandes Lima, M. A..

3 recordsLinked to original sources

bioRxiv2024

Paralemmin-1 controls the nanoarchitecture of the neuronal submembrane cytoskeleton

The Membrane-associated Periodic Skeleton (MPS) is a specialized submembrane cytoskeleton of neuronal cells, characterized by a highly ordered 190 nm periodic lattice, with emerging functions in mechanical resilience, inter- and intracellular signaling, and action potential transmission. Here, we identify Paralemmin-1 (Palm1) as a new component and regulator of the MPS. Palm1 binds to the N-terminal region of {beta}II-spectrin, a core MPS component, and is periodically organized along the axon in hippocampal neurons. Applying the 3D imaging power of MINFLUX, we locate Palm1 in close proximity (<20 nm) to the actin-capping protein and MPS component adducin. Functionally, Palm1 overexpression enhances the degree of periodicity of several MPS proteins ({beta}II-spectrin, adducin, and ankyrinB) without altering their local concentrations, while the knock-out severely compromises the MPS structure and modifies electrophysiological properties of neurons. Both the MPS-binding and remodelling activities of Palm1 are abolished by mutating a single amino acid (W54A) in the conserved Paralemmin sequence motif. Our findings identify Palm1 as the first protein specifically dedicated to organizing the MPS, and will advance the understanding of the regulation of MPS assembly and remodelling, as well as of the Paralemmin protein family.

cell biology↗

bioRxiv2023

Neuronal activity modulates the incorporation of newly translated PSD-95 into a robust structure as revealed by STED and MINFLUX

The postsynaptic density component PSD-95 undergoes activity-dependent plasticity mechanisms that rely on protein synthesis and structural remodeling. How synaptic activity can influence these dynamics at the single synapse level remains unclear. Here we combine genome-editing, pulse-chase experiments, STED and 3D MINFLUX nanoscopy on hippocampal neuronal cultures to study the integration of newly translated PSD-95 molecules at postsynaptic sites and their rearrangement within individual clusters at near-molecular resolution. We show that the amount of newly translated PSD-95 recruited to individual synapses scales with synaptic size, and modulates in a bidirectional manner, resulting in less new protein following excitatory and more new protein following inhibitory stimulation. Furthermore, we show that within synaptic clusters PSD-95 has a dispersed organization that is largely robust to long-lasting changes in activity. Altogether, this work sheds new light on the mechanisms underlying plasticity at the single synapse level, adding previously inaccessible information.

neuroscience↗

bioRxiv2022

Synaptic status differentially regulates neurofilaments in dendritic spines

Neurofilaments are one of the main cytoskeletal components in neurons and they can be found in the form of oligomers at pre- and postsynapses. How their presence is regulated at the postsynapse remains widely unclear. Here we systematically quantified by immunolabeling the occurrence of the neurofilament isoform triplet neurofilament light (NFL), medium (NFM), and heavy (NFH) at the postsynapse with STED nanoscopy together with markers of synaptic strength and activity. Our data shows that within dendritic spines neurofilament isoforms rarely colocalize with each other and that they are present to different extents, with NFL being the most abundant isoform. The amount of the three isoforms correlates with markers of postsynaptic strength and presynaptic activity to varying degrees: while NFL shows moderate correlation to both synaptic traits suggesting its involvement in synaptic response, NFM and NFH were only correlated on a low level. By quantifying the presence of neurofilaments at the postsynapse within the context of the synaptic status, this work sheds new light on the regulation of synaptic neurofilaments and their possible contribution to psychiatric disorders.

neuroscience↗