Long-distance transport is a fundamental process of life from single cell amoeba to multicellular animals. Cells have a highly organized and efficient microtubule-based transport system referred to as ‘intracellular transport’ that is dependent on microtubule associated molecular motor proteins. Microtubules are self-assembled filaments that extend from the cell centre (known as “minus-end”) towards the cell periphery (known as “plus-end”), and serve as tracks for molecular motors during intracellular transport. Members of kinesin and dynein families are mechanochemical enzymes that hydrolyze ATP to generate force and take steps along the microtubules while transporting cellular cargoes. Most kinesins transport cargoes towards the plus-end of microtubule (called as anterograde transport), whereas dyneins walk towards the minus-end of microtubule (called as retrograde transport).
Molecular motor proteins of the kinesin and dynein families have been established to play critical role in myriads of cellular processes, such as intracellular and axonal transport, viral trafficking, endocytosis, development, signaling and homeostasis. Yet the molecular mechanisms, mechanistic understanding and regulation of these motor proteins is still poorly understood, especially in direct physiological relevance. Several studies have demonstrated that presence and simultaneous activity of same or opposite polarity motor proteins is critical for generating large collective force and motility, that is essential for transporting cellular cargoes. This process is tightly regulated by cellular physiology, signalling functions and proteins, including Rab GTPases, adaptor proteins and microtubule post-translational modifications. Abnormalities in cytoskeletal elements, defects or alterations in their functions is often associated with diseases that include neurodegenerative, and developmental diseases, cancer and ciliopathies. Yet, the molecular basis of these pathologies have not been fully understood.
The aim of this Research Topic is to cover recent progress, novel research findings and limitations in the microtubule-based intracellular cargo trafficking field to understand mechanism and regulation of cargo trafficking and their implications in human pathologies.
Areas to be covered may include, but are not limited to:
- Biochemical and biophysical basis of kinesin and dynein processivity;
- Mechanisms of motor regulation, opposite polarity and cargo loading, including the presence of similar and opposite polarity motors on the same cargo and their physiological significance;
- Mechanism of microtubule-based intracellular and neuronal cargo trafficking and their regulation (e.g., Microtubules post-translational modifications);
- Structural studies of microtubule-motor and motor-cargo interactions;
- Kinesin and dynein transport in human disease.
Long-distance transport is a fundamental process of life from single cell amoeba to multicellular animals. Cells have a highly organized and efficient microtubule-based transport system referred to as ‘intracellular transport’ that is dependent on microtubule associated molecular motor proteins. Microtubules are self-assembled filaments that extend from the cell centre (known as “minus-end”) towards the cell periphery (known as “plus-end”), and serve as tracks for molecular motors during intracellular transport. Members of kinesin and dynein families are mechanochemical enzymes that hydrolyze ATP to generate force and take steps along the microtubules while transporting cellular cargoes. Most kinesins transport cargoes towards the plus-end of microtubule (called as anterograde transport), whereas dyneins walk towards the minus-end of microtubule (called as retrograde transport).
Molecular motor proteins of the kinesin and dynein families have been established to play critical role in myriads of cellular processes, such as intracellular and axonal transport, viral trafficking, endocytosis, development, signaling and homeostasis. Yet the molecular mechanisms, mechanistic understanding and regulation of these motor proteins is still poorly understood, especially in direct physiological relevance. Several studies have demonstrated that presence and simultaneous activity of same or opposite polarity motor proteins is critical for generating large collective force and motility, that is essential for transporting cellular cargoes. This process is tightly regulated by cellular physiology, signalling functions and proteins, including Rab GTPases, adaptor proteins and microtubule post-translational modifications. Abnormalities in cytoskeletal elements, defects or alterations in their functions is often associated with diseases that include neurodegenerative, and developmental diseases, cancer and ciliopathies. Yet, the molecular basis of these pathologies have not been fully understood.
The aim of this Research Topic is to cover recent progress, novel research findings and limitations in the microtubule-based intracellular cargo trafficking field to understand mechanism and regulation of cargo trafficking and their implications in human pathologies.
Areas to be covered may include, but are not limited to:
- Biochemical and biophysical basis of kinesin and dynein processivity;
- Mechanisms of motor regulation, opposite polarity and cargo loading, including the presence of similar and opposite polarity motors on the same cargo and their physiological significance;
- Mechanism of microtubule-based intracellular and neuronal cargo trafficking and their regulation (e.g., Microtubules post-translational modifications);
- Structural studies of microtubule-motor and motor-cargo interactions;
- Kinesin and dynein transport in human disease.
