Nanoscopic compartmentalization of membrane protein motion at the axon initial segment

Albrecht, David; Winterflood, Christian M.; Tschager, Thomas; Ewers, Helge

doi:10.1101/046375

Cited by 27 publications

(39 citation statements)

References 30 publications

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“…15 The barrier capacity of the AIS has also been revealed by super resolution microscopy, where 190-nm-spaced actin rings control the motion of GPI-anchored molecules at the plasma membrane. 19 Filters. The AIS also encompasses a filter that produces the segregation of somatic and axonal intracellular components.…”

Section: An Overview Of Post-golgi Vesicular Transport In the Axonmentioning

confidence: 99%

Global and local mechanisms sustain axonal proteostasis of transmembrane proteins

Cornejo

Luarte

Couve

2017

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The control of neuronal protein homeostasis or is tightly regulated both spatially and temporally, assuring accurate and integrated responses to external or intrinsic stimuli. Local or autonomous responses in dendritic and axonal compartments are crucial to sustain function during development, physiology and in response to damage or disease. Axons are responsible for generating and propagating electrical impulses in neurons, and the establishment and maintenance of their molecular composition are subject to extreme constraints exerted by length and size. Proteins that require the secretory pathway, such as receptors, transporters, ion channels or cell adhesion molecules, are fundamental for axonal function, but whether axons regulate their abundance autonomously and how they achieve this is not clear. Evidence supports the role of three complementary mechanisms to maintain proteostasis of these axonal proteins, namely vesicular transport, local translation and trafficking and transfer from supporting cells. Here, we review these mechanisms, their molecular machineries and contribution to neuronal function. We also examine the signaling pathways involved in local translation and their role during development and nerve injury. We discuss the relative contributions of a transport-controlled proteome directed by the soma (global regulation) versus a local-controlled proteome based on local translation or cell transfer (local regulation).

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Section: An Overview Of Post-golgi Vesicular Transport In the Axonmentioning

confidence: 99%

Global and local mechanisms sustain axonal proteostasis of transmembrane proteins

Cornejo

Luarte

Couve

2017

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“…Cell culture, fixation and staining Primary hippocampal neurons were cultured and immunostained as described before 32 . In short, primary mouse hippocampal neurons were plated on Poly-L-lysine coated coverslips, grown for 15 days in vitro (DIV) and fixed with 4% paraformaldehyde (PFA) plus 4% sucrose in PBS.…”

Section: Methodsmentioning

confidence: 99%

Expansion stimulated emission depletion microscopy (ExSTED)

Gao

Maraspini

Beutel

et al. 2018

Preprint

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Stimulated emission depletion (STED) microscopy is routinely used to resolve the ultrastructure of cells with a ~10-fold higher resolution compared to diffraction limited imaging. While STED microscopy is based on preparing the excited state of fluorescent probes with light, the recently developed expansion microscopy (ExM) provides sub-diffraction resolution by physically enlarging the sample before microscopy. Expansion of fixed cells by crosslinking and swelling of hydrogels easily enlarges the sample ~4-fold and hence increases the effective optical resolution by this factor. To overcome the current limits of these complimentary approaches, we here combined ExM with STED (ExSTED) and demonstrate an increase in resolution of up to 30-fold compared to conventional microscopy (<10 nm lateral and ~50 nm isotropic). While the increase in resolution is straight forward, we found that high fidelity labelling via multi-epitopes is required to obtain emitter densities that allow to resolve ultra-structural details with ExSTED. Our work provides a robust template for super resolution microscopy of entire cells in the ten nanometer range.

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“…For those two reactions we can also construct a microscopic probability density for positions x and y for the dilute case in the fashion of Eq. (6). Here the microscopic phase space only has positions for A and B particles, the C particle in reaction (30) can be placed at the origin without loss of generality.…”

Section: Generalize For Other Types Of Reactionsmentioning

confidence: 99%

Reversible Interacting-Particle Reaction Dynamics

Fröhner

Noé

2018

J. Phys. Chem. B

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Interacting-particle reaction dynamics (iPRD) simulates the spatiotemporal evolution of particles that experience interaction forces and can react with one another. The combination of interaction forces and reactions enables a wide range of complex reactive systems in biology and chemistry to be simulated, but gives rise to new questions such as how to evolve the dynamical equations in a computationally efficient and statistically correct manner. Here we consider reversible reactions such as A + B ⇄ C with interacting particles and derive expressions for the microscopic iPRD simulation parameters such that desired values for the equilibrium constant and the dissociation rate are obtained in the dilute limit. We then introduce a Monte Carlo algorithm that ensures detailed balance in the iPRD time-evolution (iPRD-DB). iPRD-DB guarantees the correct thermodynamics at all concentrations and maintains the desired kinetics in the dilute limit, where chemical rates are well-defined and kinetic measurement experiments usually operate. We show that in dense particle systems, the incorporation of detailed balance is essential to obtain physically realistic solutions. iPRD-DB is implemented in ReaDDy 2.

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Nanoscopic compartmentalization of membrane protein motion at the axon initial segment

Cited by 27 publications

References 30 publications

Global and local mechanisms sustain axonal proteostasis of transmembrane proteins

Global and local mechanisms sustain axonal proteostasis of transmembrane proteins

Expansion stimulated emission depletion microscopy (ExSTED)

Reversible Interacting-Particle Reaction Dynamics

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