Neuronal Transport

Neurofilaments [Ref: http://www.jcb.orecgi/content/abstract/160/6/817 Axonal transport of membranous and nonmembranous cargoes : a unified perspective]

• Intracellular transport is the one of the most important function of the eukaryotic cell. Nothing can function without the constant shuttling of intracellular components from place to place.
• Intracellular transport is orchestrated by a diverse constellation of molecular motor proteins that bind specific cargoes and convey them in a particular direction along cytoskeletal polymer tracks.
• Cytoskeletal polymer tracks are made up of intracellular network of filamentous structures.
• Essentially all eukaryotic cells contain 3 types of filamentous structures:

– actin filaments also k/a microfilaments

– microtubules and

– intermediate filaments.

four classes of intennediate _.filaments are found-     Keratins, Vimentin- like proteins, Neurofilaments and Lamins.

• Axons are slender cylindrical processes and can extend for distances in excess of one meter in large animals, yet they are dependent on the cell body for the synthesis of many of their components. Materials destined for the axon are transported anterogradely, toward the axon tip, and materials destined to return are transported retrogradely, toward the cell body. This bidirectional transport process, known as axonal transport, is not fundamentally different from the pathways of macromolecular and membrane traffic that occur in all eukaryotic cells, but it is remarkable for its scale.
• Proteins and other molecules are transported along axons in association with distinct membranous and nonnzembranous cargo structures that move at different rates. Membranous organelles move most rapidly, in the fast components of axonal transport, whereas cytoskeletal polymers and cytosolic protein complexes move more slowly, in the slow components.
• Membranous organelles like endocytic vesicles, lysosomes, golgi body derived vescicles are the principal cargoes of fast axonal transport. The many proteins, lipids, and polysaccharides that move along the axon at fast rates do so by virtue of their association with one or more subclasses of organelle or vesicle, either because they are sequestered within its lumen, embedded in its membrane, or bound to its surface.

Membranous organelles move along both microtubule and microfilament tracks powered by molecular motor proteins (kinesins, dyneins, and myosins). Microtubules appear to be the principal tracks for long-range movements along the axis of the axon.

Plus end–directed kinesin motors propel organelles along microtubules anterogradely, whereas dynein (and possibly also minus end–directed kinesin motors) propel organelles retrogradely.

• Non membranous cargoes like cytoskeletal polymers (microfilaments, microtubules and neurofilaments) and cytosolic protein complexes move more slowly, in the slow components.
• It was earlier believed that the fast and slow axonal transport are due to fundamentally distinct mechanisms of transport. But recent discoveries have shown that the underlying mechanism for both fast and slow transport is.the same. They move at different rates due to difference in their duty ratio. The duty ratio is the proportion of time that a cargo structure spends actually moving. Thus the slow overall rate of movement of cytoskeletal filaments suggests that these structures move with a low duty ratio, spending most of their time not moving.

B i.e. Dynenin and kinesin

Microtubules guide the transport of protein & vesicular material; and ‘Motors’ (Denin & Kinesin) provide the force behind such movementQ

Molecular Motors

Molecular motors are ATPase that move proteins, organelles, and other cell parts (their cargo) to all parts of the cells.

C i.e. Neurofilament

Axonal transport of membranous & non membranous cargoes

• It is now known that intracellular transport is coordinate by molecular motor proteins that bind cargoes and convey them in a particular direction along cytoskeletal polymer tracks. This includes every type of membranous organelle and transport vesicle (membranous cargoes), as well as nonmembranous cargoes such as cytoskeletal polymers, cytosolic protein complexes, ribosomes, and messenger RNAs.
• Membranous organelles move most rapidly, in the fast components of axonal transport, whereas nonmembranous cytoskeletal polymers and cytosolic protein complexes move more slowly, in the slow components. Recent studies suggest that slow axonal transport is generated by fast motors and that the slow rate is due to rapid movements interrupted by prolonged pauses.
• Materials destined for the axon are transported anterogradely, toward the axon tip, and materials destined to return are transported retrogradely, toward the cell body. This bidirectional transport process, known as axonal transport, is not fundamentally different from the pathways of macromolecular and membrane traffic that occur in all eukaryotic cells, but it is remarkable for its scale
• Membranous organelles are the principal cargoes of fast axonal transport. The many proteins, lipids, and polysaccharides that move along the axon at fast rates do so by virtue of their association with one or more subclasses of organelle or vesicle, either because they are sequestered within its lumen, embedded in its membrane, or bound to its surface.
• Both neurofilaments and microtubules move at fast rates, approaching the rate of movement of membranous organdies, but the average rate of movement is slow because the movements are both infrequent and bidirectional. Thus, the overall speed and direction of neurofilament and microtubule movement is a temporal summation of anterograde and retrograde movements and pauses, perhaps not fundamentally dissimilar from the behavior of mitochondria in axons described above. As is the case for mitochondria, the slow overall rate of movement of neurofilaments and microtubules suggests that these structures move with a low duty ratio, spending most of their time not moving.
• The rapid rate of movement of neurofilaments and microtubules in axons indicates that they are transported by fast motors, perhaps similar or identical to motors that move membranous organelles. Several lines of evidence suggest that dynein may transport axonal microtubules anterogradely, perhaps relative to the microfilament matrix, and that dynein and kinesin may transport axonal neurofilaments bidirectionally along microtubules by the same mechanism that is thought to move vimentin along microtubules in nonneuronal cells
• Cytoskeletal proteins have been the exclusive focus of studies on slow axonal transport in recent years, but it is important to remember that several hundred other proteins also move in this rate group, representing the entire spectrum of cytosolic proteins that comprise axoplasm. Some examples include proteins involved in vesicle dynamics such as clathrin and synapsin; regulatory proteins such as calmodulin; metabolic enzymes such as creatine kinase, aldolase, and enolase; cytoskeletal proteins such as spectrin, tau, and dynactin; and motor proteins such as dynein and myosin
• Cytoskeletal polymer tracks are made up of intracellular network of filamentous structure. All eukeryotic cells have 3 types of filaments – Microfilaments (actin filaments)

• – Microtubules (tubulin filaments)

  – Intermediate filaments has 4 classes: keratins, neurofilaments, lamins and vimentin like proteins