Neurocytology

Kandel

Chapter 4

Alberts,

Molecular Biology of the Cell,

Chapter 12

Neurons resemble epithelial cell, except for their shape

Organelles inside neurons are almost the same as in any other cell

Only plants

• Neuronal structures:

– Nucleus– Cell body cytosol– Dendrites– Axon

Outside the nucleus:

• Ribosomes (CB and D)• Rough Endoplasmic Reticulum (CB and D)• Golgi complex (CB and D)• Lysosomes (CB and D)• Peroxisomes (CB and D)

• Mitochondria (CB, D and A)• Smooth Endoplasmic Reticulum (CB, D and A)

The nucleus

has a double membrane with nuclear pores for the traffic of macromolecules:

Transcription factors and Nucleic acids

Proteins are synthesized from mRNA synthesized in the nucleus and translocated to ribosomes

A specific transport mechanism is responsible for mRNA traslocation

An active transport system using GTP energy traslocates macromolecules in and out from the nucleus

Nuclear pores are typically made up by 8 subunits

RIBOSOMES

Are produced in the nucleolus and transported to the extracllular space where some of them are taken by the endoplasmic reticulum (ER)

Ribosomes are not organelles, in the sense that do not have an internal and external sides separated by a lipid membrane. They are made up by two subunits. Their total composition is 2/3 RNA and 1/3 proteins

Complex mechanism of protein synthesis and folding

Once they are in the extranuclear space part of the ribosomes stay free in the cytosol, and part of them stick to the Endoplasmic Reticulum (ER)

The ER has two compartments: the “rough” ER and the “smooth” ER.

The rough ER is characterized by the presence of long lines of ribosomes that are continuously producing proteins and sending them to other organelles

Endoplasmic Reticulum

Specific intracellular stimuli induce the release of Ca+2 from the ER

There are two separate Ca+2 stores:

1) IP3-gated

2) Ca+2-gated(Ryanodine-dependent)

Their activation transiently elevates [Ca+2]i, the cytosolic concentration of Ca+2

Another function of the Endoplasmic Reticulum:

Ribosomes in Cell Body

and Dendrites

Once proteins are synthesized and folded they detach from ribosomes but are not ready yet to function, and need to be properly folded and further modified

Golgi apparatus

Transmembrane protein can cross the membrane many times

A series of enzymes starts to modify proteins when they are being synthesized (co-translational modifications)

Post-translational Modifications• Thioacylation - anchors to membrane– GAD, SNAP25, and GAP-43

• Isoprenylation - anchors to membrane– Ras and Rab GTPases

• Ubiquitin - Degradation • Glycosylation – NCAM

• Phosphorylation of Serine Threonine & Tyrosine

– Rapid modification of enzyme activity

Other modifications are performed after their synthesis

Complex sugar chains are attached as a whole in the ER

Lipids are attached sometimes to the end of the protein, as an anchor to the cell membrane lipid bilayer.Sugar-lipid chains characterize extracellular proteins like Ach-esterase or NCAM cell adhesion molecules

Successive stages of further proteins modifications are performed in the Golgi apparatus, up to the transport of complete, functional proteins at their site of work

Even after proper folding and posttranslational modification they are often not ready yet and need to be assembled in various subunits, like for instance many membrane channels

DNA Protein

InactiveProtein

Inactive mRNA

Primary RNA

transcriptmRNAmRNA

1Transcriptional

Control

2RNA Processing

Control

4Translation

Control

5mRNA

DegradationControl

6Protein ActivityControl

3RNA Transport

Control

CytosolNucleus

Gene expression can be controlled by regulating mRNA stabilityThe competition between mRNA translation and decay might be related to synaptic plasticity