Cellular biology of neurons

The human brain consists of more than 10 ¹¹ neurons associated with more than 10 ¹² glia cells. A neuron is an electrically excitable cell that processes and transmits information via electrical and chemical signals. Each morphological part of the neuron has a separate signaling function (separate biochemical reactions) and is of ectodermal origin, as are the epithelial cells. We distinguish the following functional structures on neurons:

• Dendrites and axons are input or receptive, which translates signals into intracellular biochemical signals (the membrane corresponds to the basolateral membrane of epithelial cells).
• Trigger zone nerve impulse is an axonal mound in which all received excitatory impulses are integrated and further translated along the axon.
• The conduction part of a neuron is an axon that conducts an impulse to the next neuron, i.e., to the synapse
• presynaptic element is the presynaptic part of a neuron (the membrane corresponds to the apical membrane of epithelial cells), where a neurotransmitter transmits a signal in the form of signaling molecules uni-directionally to the postsynaptic part of another neuron, which is connected by a synapse (synapse is asymmetric or polarized, leading to unidirectional transmission).

Neurons are terminally differentiated because they no longer divide after formation. The neuron’s nucleus is pale because the chromosomes are not compact, and the nucleus is visible.
Neurons synthesize three major groups of proteins:

1. Cytosolic proteins for the cytoskeleton and numerous enzymes characteristic of certain neurons (acetylcholine neurons contain choline acetyltransferase, chAT)
2. Proteins formed in the cytosol that are further distributed in the nucleus, mitochondria, and peroxisomes
3. Proteins in function cell membranes :

The mRNA molecule

The mRNA molecule, which controls the synthesis of groups 1 and 2, is bound to polyribosomes, while the mRNA of the third group is located in the rER membrane. All proteins (except mitochondria) are formed on ribosomes in the cytosol, and depending on whether they have an amino acid signal sequence, remain in the cytosol or are further broken down into the nucleus through nuclear pores, through the membrane by carriers into the lumen of the organelle or vesicular transport. A neuron can release content into its environment through the process of exocytosis. During the endocytosis process, it can enter the content and further distribute it with the help of endosomes and lysosomes (the path of biosynthesis and secretion). ER and GA form a system of cisterns and cavities. Sometimes, a set of flattened and strongly perforated cisterns is observed along the edge of the cytoplasm à hypolemal cistern (Probably all neurons have it, but it is well visible in Purkinje fibers). Cisterns along the very edge of the membrane can also be seen, which, if found below the synaptic membrane, are called subsynaptic tanks. ER is the center of protein and most lipid synthesis and contains calciosome by storing Ca ions. Covalent addition of sugar (pre-prepared N-linked oligosaccharide from dolichol is transferred to the NH2-group of asparagine by oligosaccharyltransferase) to proteins is one of the main biosynthetic functions of ER.

Golgi apparatus

Golgi apparatus is the major site of carbohydrate synthesis and classification of the content received from the ER, and consists of the cis network (facing the core, more hollow), the Golgi stack (cis and trans subdivision), and the trans (facing the st membrane) network. Proteins are further processed in GA, and you can find two large groups of N-linked oligosaccharides on glycoproteins:

1. Complex oligosaccharides contain more than two initial molecules of N-acetylglucosamine (obtained in ER) and a diverse number of residues of galactose, galactose, and sialic acid (has a negative charge).
2. Oligosaccharides with a high mannose content contain only two original molecules of N-acetylglucosamine and numerous mannose residues.

Lysosomes

Lysosomes serve the intracellular digestion of macromolecules. Their pH is about 5. It contains over 40 hydrolytic enzymes, H-pumps insert protons into the cytosol of lysosomes. Macromolecules reach them through autophagosomes, phagosomes, or endosomes. The contents are introduced into the cell from the outside by intussusception with endocytosis. We differentiate pinocytosis (in the intake of less liquid or dissolved content) I phagocytosis (intake of larger molecules). Neurons use pinocytosis, where they first form clathrin-coated vesicles, which fuse with early endosomes and form a late endosome that fuses with lysosomes. Neurons often have receptors (transmembrane proteins) to which molecules bind and enter as receptor complex – macromolecule. Some molecules remain bound to receptors. The recycling processor can expel them into a new cell membrane’s lysosomes and participate in the transcytosis process. Neurons process controlled exocytosis (controlled secretion pathway) store molecules derived from GA in the form of clathrin-coated vesicles (protein or smaller molecules) in secretory and synaptic vesicles, which are secreted in response to some external specific signal (constitutional exocytosis – used by all cells).

A neuron can act as an endocrine cell or as a neuron because it can secrete, e.g., oxytocin or vasopressin, into the bloodstream (hormone) or at the end of the axon at the synapse (neurotransmitter). This phenomenon is called neurosecretion/ neurosecretory cell / neurosecretory granules or vesicles. Most proteins are first synthesized as inactive precursors, which are subsequently proteolytically processed (cleaved into biologically active peptides) during travel through the trans-Golgi network, secretory vesicles and in the extracellular fluid (pre-pro-protein is cleaved in ER and pro-protein is formed, which is cleaved again before exocytosis into a secretory polypeptide). Secretory vesicles transfer content from the ER and GA to the axon’s presynaptic portion, where they are stored, and then empty bubbles travel back to be refilled ( axonal transmission ). Synaptic vesicles form where the secretory ones, but they are refilled locally, i.e., at the axon’s very end.

According to the type of vesicle coat, we distinguish two types of vesicles:

1. Clathrin-coated vesicles – selective transmission of transmembrane receptors. Clathrin (3 large and three small subunits) forms a triskelion basket, and they combine into a basket network. Clathrin provides the necessary mechanical force to separate the vesicle and ensures that the contents remain in a separate compartment, i.e., vesicles. The receptor-ligand complex participates in the fusion of the vesicle with the membrane and stabilization adaptin and the “separating” ATPase in separating the mantle from the vesicle.
2. Catrin-coated vesicles – non-selective transmission between ER and GA

The transfer of vesicles is controlled by GTP-binding proteins, monomeric GTPases, or polymeric GTPases (having multiple polypeptide chains). The active form has bound GTP and the inactive GDP.

Cytoskeleton

Cytoskeleton allows the cell to migrate, transfer proteins (builds “roads”), move organelles and shape an individual neuron. All of these functions work with helper proteins. The cytoskeleton is made up of three types of protein filaments:

• actin or microfilaments are made of actin, form polar, spherical polymers, and are essential for cell movement. They function as nets or bundles. They form the cell cortex and are especially pronounced in the dendritic joints. Actinium allows their interaction with the extracellular matrix.
• Microtubules (microtubules) are made of tubulin (polymerization) and form the cytoskeleton’s backbone. Each monomer binds 2 molecules of GTP or one GTP and one GDP molecule, which bind to the β-subunit of tubulin (hydrolysis of GTP leads to depolymerization). Microtubules grow by the process nuclei (slower) or process extensions. They distinguish between the plus (fast-growing) and minus (slow-growing) end, which can be stabilized by a centrosome (centriole surrounded by a centrosome matrix). They are located in dynamic instability because they are constantly growing and shrinking, and individual tubulin molecules, whose lifespan is about 20 hours, participate in the construction of more mirkotubu. MAP proteins participate in microtubule stabilization and fetal neuron differentiation. MAP-1 is present in axons, and MAP-2 in catfish and dendrites.
• Intermediate filaments are non-polar polymers made of vimentin or lamin (elongated fibrous molecules with a head – amino end and tail – carboxy end and with the dreadlocks, which connects the head and tail) and give mechanical resistance to the cell, and we divide them into three groups:

1. Keratin filaments – epithelial cells, nails, and hair
2. Vimentin filaments – vimentin, desmina (muscles), and acidic fibrous glia proteins – GFAP (astrocytes and Schwann cells).
3. Neurofilaments – subunits are NF-L (low weight), NF-M, and NF-H (medium and high weight, present in axons and forming continuous ˝ narrow˝ lengths 1m). Silver impregnation methods paint them.

Motor proteins

Motor proteins enable organelles’ movement by constant hydrolysis of ATP and by pulling organelles along microtubules or actin filaments (kinesins – go towards the + end, cytoplasmic and ciliary dyneins – go towards the perm – end). They consist of two heavy (ATPases) and several light chains to tie their load. Proteins and organelles are transported along axons in both directions:

1. Rapid anterograde transmission of newly synthesized ER and cell membrane materials, synaptic components, and vesicles – from the soma to the presynaptic part of the axon.

• Type I – 100-400 mm / day
• II. species – 20 – 70 mm / day
• III. species – 3 – 20 mm / day

1. Slow anterograde transmission components (0.1 – 4 mm / day) of the cytoskeleton and associated proteins, cytosolic enzymes of intermediate filaments. It serves to replace worn-out structural proteins. At a rate of 0.2 – 2.5 mm / day, subunits of neurofilaments and microtubules are transmitted. At a rate of 3-4 mm / day, molecules of the cytoskeleton and associated molecules and some enzymes.
2. Retrograde transmission takes place at a speed of 300 mm/day. The content is transferred to the catfish, i.e., into lysosomes and contents for re-metabolic use. It matures this way NGF (neurotrophic growth factor), enzyme HRP and neurotropic viruses (herpes simplex, rabies, and poliovirus).

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