L12: Molecular motors II Flashcards
diverse cellular functions of cytoskeletal motor proteins?
▪ Organelle / vesicular transport
▪ Muscle contraction
▪ Cilia and Flagella
▪ Chromosome separation in mitosis
▪ Cell migration
vesicular/organelle transport by microtubule-based motors?
Microtubule Network Organization:
Microtubule organizing center (MTOC) is located near the nucleus.
Minus (-) end of microtubules is anchored near the nucleus/MTOC.
Plus (+) end extends towards the cell periphery.
Forms unidirectional highways for intracellular transport using motor proteins.
Motor Proteins & Direction of Transport:
Kinesins → Move cargo towards the plus (+) end (cell periphery).
Kinesin-1 is the most well-studied, but Kinesin-2 and Kinesin-3 also contribute.
Dynein → Moves cargo towards the minus (-) end (MTOC/nucleus).
Cytoplasmic dynein is responsible for nearly all minus-end-directed transport.
Organelle Positioning:
Golgi is typically localized near the nucleus (minus-end region).
ER extends towards the cell periphery (plus-end region).
Both structures are pulled by motors along the microtubule network.
Bidirectional Vesicle Transport:
Vesicles can switch between kinesin and dynein, leading to bidirectional movement.
Ensures dynamic transport and positioning within the cell.
models for bidirectional transport?
Models for Bidirectional Transport
Tug-of-War Model
Kinesin (plus-end) and dynein (minus-end) motors are attached to the same vesicle.
They compete, pulling in opposite directions.
The stronger/more active motor wins, determining movement direction.
Example: If dynein wins, transport is retrograde (toward the nucleus).
Biochemical Coupling Model
Motor activity is coordinated rather than competitive.
Regulation occurs through direct interactions or signaling pathways.
Ensures controlled switching between kinesin and dynein activity.
Regulation of Motor Activity
Enzymes and signaling pathways modulate motor activity.
Example: If a vesicle needs to move toward the plus-end, kinesin is activated.
Once it reaches the target, kinesin is inactivated, and dynein is activated to move it back.
axonal transport?
axonal transport in neurons driven by molecular motors.
dendrites recieve synaptic inputs and terminal braanches of axon make synapses on target cells.
Neurons require molecular motors to transport essential components to different parts of the cell, ensuring synaptic functionality.
Bidirectional Transport in Axons
Axonal microtubules are uniformly oriented:
Minus-end → Towards the cell body
Plus-end → Towards the growth cone
Microtubules are parallel bundles along the axon.
Dynein and kinesin transport specific vesicles containing neurotransmitters (NTs).
These vesicles bind both dynein and kinesin but only one motor is active at a time.
Mechanism of Vesicle Transport
Anterograde transport (towards growth cone)
If a vesicle starts from the cell body, kinesin is activated and drives transport along the microtubule toward the growth cone.
Turnaround Zone (Switching Motors at the Synapse)
When the vesicle reaches its target, kinesin is switched off, and dynein takes over.
This region, called the turnaround zone, ensures biochemical regulation of transport.
Retrograde transport (back to the nucleus/cell body)
Dynein is activated, moving the cargo back toward the cell body.
Regulation of Motor Activity
Dynein is carried in a repressed form during anterograde transport.
At the turnaround zone, dynein is activated, and kinesin is repressed, allowing transport in the opposite direction.
Example: Prion Protein Vesicle Trafficking
The movement of prion protein vesicles in neurons is regulated by dynein and kinesin, following this bidirectional transport system.
kinesin-mediated anterograde transport?
Kinesin-mediated anterograde transport important for axon elongation and synaptogenesis
axon long structure.canot rely on diffusion of components so need specificity by motors. Kinesins drive cargo for shipping. eg: need mRNA transported by kinesin-5/. Mitochondria, vesicles. For synapsis assembly. Delivered by kinesin along the microtubule.
Anterograde microtubule-dependent
movements of membranous organelles
and RNA granules are supported by
various plus-end-directed kinesin motors.
Organelles such as mitochondria,
vesicles, RNA are transported from the
soma toward axon tip during axonal
growth and synapse formation
Any defect in motor function would cause disruption.
Defects in neuronal motor trafficking may contribute to neurodegenerative disease
Mutations of kinesin motors are associated with a spectrum of neurodegenerative diseases
organelle transport by microtubule-based motors?
The position of the Golgi apparatus is controlled by microtubules and motors
Localised around nulceus by microtubule network?
When microtubule experimentally depolymerised golgi system becomes scattered in the cell. Shows their importance in organelle positioning.
trafficking of melanosomes?
Trafficking of melanosomes uses kinesin-1, dynein and myosin V
Retrograde- dynein
Anterograde-kinesin
Controlled by level of cyclic amp (cAMP)
Dispersed phenotype- vesicles all scattered to aggregated where vesicles are focused around nucleus in one spot. Driven by molecular motors. Dynein and kinesin both attached to these vesicles.
When camp high then both active. Kinesin winning. Motion anterograde. Drag vesicles towards cell periphery. When levels of camp decrease, kinesin inactivation (biochemical reg) so dyenin drives motion of vesicle around cell nuclei. Aggregated.
Melanosomes are organelles that contain the pigment melanin.
They are produced in melanocytes and transported to the cell periphery, where they are transferred to neighboring keratinocytes or photoreceptor cells in mammals.
Kinesin and dynein facilitate long-distance transport of melanosomes.
Myosin V helps melanosomes navigate the actin barrier at the cell cortex.
Reversible melanosome transport occurs in leucophores/melanophores (depending on context).
When melanosomes reach the actin cortex, Myosin V is involved in their anchoring and movement.
motor ensembles in muscle?
From single motors to motor ensembles: thick filaments in striated muscle
Thick filaments in striated muscle (cardiac and skeletal) are specialized for force generation and muscle shortening.
The main motor driving sarcomere shortening is myosin II.
Myosin II consists of:
Two heavy chains, each containing a motor domain that extends into the tail domain.
Two pairs of light chains: regulatory and essential.
The tail domain allows myosin molecules to polymerize and form thick filaments.
Myosin II forms bipolar filaments, where:
Motor domains protrude in an array from the filament surface.
The central region consists only of tail domains.
On either side, myosin motors are arranged in an antipolar fashion.
Dimers of myosin assemble into bipolar thick filaments, facilitating contraction.
what do thick filaments enable in striated muscle?
Thick filaments enable sarocmere shortening and force production in striated muscle
In the muscle sarcomere
myosin filaments are
overlapped by two sets of antiparallel actin filaments
Myosin II motors on the
thick filaments pull the
actin filaments towards
the middle of the
sarcomere
Myosin II motors on thick filaments pull actin filaments toward the center of the sarcomere, causing muscle contraction.
The sarcomere is the fundamental contractile unit of striated muscle.
Thick filaments (which contain myosin II) are anchored at the M-line, the central region of the sarcomere.
Thin filaments (actin) are anchored at the Z-disc, which marks the boundaries of a sarcomere.
When myosin pulls actin toward the M-line, the sarcomere shortens, leading to muscle contraction.
The sarcomere structure amplifies force production and shortening, as multiple myosin motors work together within each sarcomere.
axenomal dyneins?
Axonemal dyneins drive the movement of cilia and flagella by generating force along microtubule doublets.
The axoneme, the core structure of cilia and flagella, follows a “9 + 2” arrangement:
9 microtubule doublets form a ring around a central pair of microtubules.
The doublets are transversely linked by cross-links and dynein arms, which bridge neighboring microtubules.
Dynein motors attempt to slide the microtubules past each other, but cross-links (nexin links) prevent sliding.
Instead of sliding, the dynein-induced force results in bending, which produces the characteristic wavelike motion of cilia and flagella.
Coordinated bending generates the swinging motion seen in structures like the sperm flagellum, allowing movement.
*chatgpt
