Transcript
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
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