11 MZB I - Mansuy

Most impulses arise at the junction of the axon hillock and initial segment 

The cytoplasm = axoplasm

 The plasma membrane = axolemma

Anterograder Transport
-> Vom Zellkörper zur Synapse (anterograd, stromabwärts)
Retrograder Transport
-> In der umgekehrten Richtung (retrograd, stromaufwärts) 

Type of Tranport:      Speed                     Transported Materials:
Fast Anterograde      50-500mm/day       Vesicles and Organelles
Slow AAnterograde   0.1-10 nm/day        Cytosskeleton, soluble Proteins, Enzymes
Fast Retograde         200-500 mm/day    Lysosomes, Organelles, Soluble Proteins

- Microtubule-based movement
- Actin-based movement
- Membrane trafficking

Long-distance transport mediated by molecular motors, kinesin and dynein that use microtubules as tracks

Short-distance transport usually mediated by myosin motors that use actin filaments as tracks

Myosins are molecular motors that move cargo along actin filaments

Synaptic regions contain a molecular machinery for protein synthesis, protein modification, membrane insertion (at the synapse and extrasynaptically), membrane retrieval, and membrane recycling

Structural support and plasticity of the neuronal framework

Provides the equipment for transport within the cell

Microtubules (25nm) 
-> Tubulins, MAPs, motor proteins: kinesins and dyneins

Microfilaments (5-9nm)
-> Actins, actin monomer binding proteins, capping proteins, gelsolin family, crosslinking and bundling proteins, tropomyosin, motor protein: myosin

Intermediate filaments (10nm) (Superfamily of 5 types)
Types I and II: keratins
Type III: GFAP, vimentin, desmin, peripherin
Type IV: internexin, nestin (neurofilaments)
Type V: nuclear lamins

Mikrotubuli sind röhrenförmige intrazelluläre Polymere aus globulären Tubulinuntereinheiten. DieProteinstrukturen haben einen mittleren Durchmesser von 24 nm und bilden zusammen mit denMikrofilamenten und den Intermediärfilamenten das Zytoskelett, welches der Zelle Form und Festigkeit verleiht.

Mikrotubuli sind aus α- und β-Tubulindimeren (Heterodimere) aufgebaut.
->There are three α-tubulins and five β tubulins 
    -> The properties of microtubules depend on the tubulin isoforms they are made of

Tubulin subunits are subjected to many posttranslational modifications (tyrosination, acetylation, polyglutamylation , polyglycylation , phosphorylation, palmitoylation) when incorporated into microtubules
-> Posttranslational modifications determine the diameter and spatial distribution of the tubules

s.B.

Microtubule-Associated Proteins (MAPs)

- MAPs belong to a heterogeneous group of proteins
- They attach to the surface of microtubules to increase their stability and promote their assembly
- MAPs are regulated by phosphorylation at specific amino acid residues
- Most MAPs that have been identified are found only in brain tissue
- Tau is a highly phosphorylated MAP that is associated with Alzheimer’s disease.

Kinesins and dyneins

Enzymes that convert ATP hydrolysis directly into movement along cytoskeletal filaments: Generate force

Carry cargo (organelles, protein complexes, RNA) and mediate microtubule/microtubule sliding
-> Different types of cargos move at different speed along the axon (‘slow’ versus ‘fast’ axonal transport)

Some motors move towards the + end, others to the - end

Movement can be anterograde or retrograde, and uses different motor proteins
-> Kinesins move cargo antero- and retrogradely while dynein moves cargo retrogradely

(Anterograd bedeutet "nach vorne gerichtet". Damit kann eine zeitliche oder räumliche Dimension gemeint sein.

Retrograd bedeutet "rückläufig", zeitlich oder örtlich "zurückgesetzt" oder "in entgegengesetzter Richtung".)

Kinesin superfamily proteins (KIFs) bind to cargoes through adaptor or scaffolding protein complexes

Role: Delivery of cytosolic, cytoskeletal and other proteins to nerve terminals

Two Major “Slow Components (SC)” :
1. SCa: Transport of microtubules and associated proteins, spectrins, neurofilaments. Speed: 0.31-3 mm/day
2. SCb: Transport of actin, clathrin, enzymes and many other proteins. Speed: 2-8 mm/day

Transport and delivery of organelles such as mitochondria and vesicles, and plasma membrane proteins to the nerve terminal. Speed: 200-400 mm/day (~2-5 µm/sec)

Retrograde movement of vesicles i.e. containing neurotrophic factors back to the cell body. Transport of endosomes, lysosomes, internalized receptors, neurotrophins. Speed: 200-400 mm/day