Endocytosis in the AIS is necessary for the maintenance of dendritic protein polarity.
A, Morphology of neuron (A neuron, or nerve cell, is an excitable cell constituting the functional unit…) PVD in C. elegans. Dendrites are very long and branched, while axon does not branch. In the AIS, identified with various markers, the dots mark the protein (A protein is a biological macromolecule composed of one or more…) dendritic (DMA-1) endocytosed.
B, In a neuron of rat (The word “rat” designates in French, in the vernacular…)dendritic protein-containing endocytosis events occur in dendrites and soma (cross blue (Blue (from Old High German “blao” = brilliant) is one of the three colours…) clear) and the SIA (yellow crosses) but very little in the axon.
C, In human neurons, after blocking endocytosis, dendritic proteins, normally not present in the axon, become detectable in the axon.
D, Diagram of the three cellular mechanisms that maintain polarity in neurons. The third mechanism, endocytosis in the AIS, is revealed in the study by Eichel et al.
© David Perrais
Neurons, the main cells of the brain (The brain is the main organ of the central nervous system of animals. The brain processes…)are very polarized cells, that is to say they are formed of two very different parts: on the one hand the axon, a very fine tubular compartment (less than 1 µm in diameter) which can reach for some neurons a length (The length of an object is the distance between its two furthest extremities…) of several cm or even nearly one metre (The meter (symbol m, from the Greek metron, measure) is the basic unit of length of…). The axon allows the transmission of electrical signals to target neurons through synapses. On the other hand, the cell body and the dendrites, which make up the “receiving” part of the neuron, where there are many synapses formed with other neurons. The electrical signals from the synapses are combined and then, if they are large enough, will cause the generation of an action potential at the level of an intermediate compartment between the axon and the soma called the initial segment of the axon (AIS).
In addition to its role in generating action potential, SIA play (The cheek is the part of the face that covers the oral cavity, closed by the…) a very important role in preserving the polarization (the polarization of electromagnetic waves; the polarization due to moments…) neurons. Indeed, the constituent elements of the axon or the dendrites/soma, in particular the proteins, are very different. Neurons have, at the level of the AIS, mechanisms allowing the sorting of cellular elements in order to guarantee this polarity. So far, scientists have been able to demonstrate two cellular mechanisms for preserving polarity. First, the vesicles of transportation (Transportation is the act of carrying something, or someone, from one place to another, the most…) intracellular are sorted at the level of the SIA: those transporting the axonal proteins pass a filtered (A filter is a system for separating elements in a stream.) located in the AIS while vesicles carrying dendritic proteins enter the AIS but cannot pass (The genus Passer was created by the French zoologist Mathurin Jacques…) the filter and turn around. Second, the proteins located on the plasma membrane (The plasma membrane, or plasmalemma, is the membrane that delimits a cell, it…) to the surface (A surface generally refers to the superficial layer of an object. The term a…) neurons diffuse into the membrane but the AIS also has a barrier of diffusion (In everyday language, the term diffusion refers to a notion of…) which makes it possible to filter the dendritic surface proteins by preventing them from diffusing into the axon.
As part of a collaboration with theUniversity (A university is an institution of higher education whose objective is the…) from Stanford in California, scientists from the CNRS (The National Center for Scientific Research, better known by its acronym CNRS, is the largest…) identified a third mechanism for preserving the polarity of neurons: the internalization of dendritic surface proteins by endocytosis and their degradation in the AIS. To reach this conclusion, they used three biological models. All (The whole understood as the whole of what exists is often interpreted as the world or…) first, they studied certain neurons in the worm (Worms are a very heterogeneous group of invertebrate animals…) nematode Caenorhabditis elegansa millimeter-long worm that is one of the most studied model systems by biologists.
By focusing their study on one of the worm’s 302 neurons, the scientists showed that this neuron has an AIS and that blocking endocytosis specifically in this neuron causes the redistribution of a dendritic surface protein called DMA- 1 to the axon. Moreover, this protein, which is responsible for the formation of dendritic branches, causes the ectopic formation of branches normally absent in the axon when present in the axon. They also showed that endocytosis plays the same role for dendritic surface proteins in human neurons, as well as in rodent neurons.
The scientists also directly visualized the endocytosis of the AIS using a method ofimagery (Imagery is primarily the making and trading of physical images that…) by fluorescence (Fluorescence is a light emission caused by the excitation of a molecule…) to detect the formation of endocytic vesicles in time (Time is a concept developed by human beings to apprehend the…) real (see Sposini et al. 2020) to show that dendritic surface proteins are indeed internalized in the AIS of neurons, and that the frequency (In physics, frequency generally refers to the measurement of the number of times a…) of endocytic vesicle formation is the same as in dendrites.
These results constitute an important advance in the understanding of the cellular mechanisms of formation and preservation of neuronal polarity. They will also make it possible to study this new form of endocytosis and to determine its specific mechanisms, which could lead to a better understanding of the functioning of AIS, an essential compartment of neuronal function.
To know more:
Endocytosis in the axon initial segment is a clearance mechanism to maintain neuronal polarity.
Eichel K, Uenaka T, Belapurkar V, Lu R, Cheng S, Pak JS, Taylor CA, Südhof TC, Malenka RC, Wernig M, Özkan E, Perrais D, Shen K.
Nature August 17, 2022. https://doi.org/10.1038/s41586-022-05074-5
Imaging endocytic vesicle formation at high spatial and temporal resolutions with the pulsed-pH protocol.
Sposini, M Rosendale, L Claverie, Van TNN, D Jullie, D Perrais.
Nature Protocols September 2020 DOI: 10.1038/s41596-020-0371-z
Institute Interdisciplinary (Interdisciplinary work incorporates concepts from different disciplines.) of Neuroscience (The neurosciences correspond to the set of all biological disciplines and…) (CNRS/University of Bordeaux). Broca New Aquitaine building. 146 street (The street is a circulation space in the city that serves housing and places…) Leo Saignat.
French version (674.92 KB)
David Perrais- Searcher (A researcher (fem. researcher) refers to a person whose job is to do research…) CNRS atInstitute (An institute is a permanent organization created for a certain purpose. It is…) interdisciplinary of neurosciences (CNRS/University of Bordeaux) – david.perrais at u-bordeaux.fr
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