26.7:
The Movement of Organelles and Vesicles
Microtubules form a network of filaments in eukaryotic cells that act as railway tracks to transport organelles and vesicles by the microtubule-associated motor proteins— kinesin and dynein.
Kinesins carry mitochondria and secretory vesicles towards the cell periphery, while dyneins position the Golgi apparatus near the cell center.
In the hand-over-hand model, the two globular heads of the kinesin move alternately forward, resembling a walking movement.
ATP is bound to the kinesin, and its hydrolysis powers the forward motion of the rear globular head.
Upon binding to the microtubule, the kinesin releases the ADP, and an ATP quickly occupies the recently vacated nucleotide-binding site to power the next movement.
In contrast, the inchworm model hypothesizes that the front and rear globular heads of kinesin do not switch places during the movement. During each cycle of progressive forward movement, hydrolysis of a single ATP takes place only at one of the globular heads.
During transport, cytoplasmic dyneins associate with another large protein called dynactin, which has a short actin-like filament, Arp1. Arp1 acts as a receptor for attaching the motor protein complex to the vesicles. This attachment results in the hydrolysis of ATP, causing the complex to move.
26.7:
The Movement of Organelles and Vesicles
In eukaryotic cells, cytoskeletal filaments such as actin, microtubules, and intermediate filaments form a mesh-like cytoskeletal network. These filaments serve as tracks for transporting cellular cargo. Specialized motor proteins use the chemical energy stored in adenosine triphosphate (ATP) for this transport. During interphase, microtubules are polarized, with the plus-end towards the cell periphery and the minus-end towards the cell center. Two microtubule-associated motor proteins, kinesin and cytoplasmic dynein, transport organelles and vesicles.
Transport via kinesins
Kinesin is a plus-end-directed, microtubule-associated motor protein made up of two heavy chains and two light chains. Kinesin motors are highly efficient as they undergo hundreds of ATP hydrolysis cycles without dissociating from the microtubules while transporting cellular cargos. During interphase, kinesins transport organelles and vesicles across the cell. The kinesins attach to specific vesicles or organelles with the help of the receptor domain present in its light chain. Some kinesin motor proteins have also shown preferential binding for post-translationally modified microtubules. For example, acetylation and detyrosination of microtubules alter the binding and mobility of kinesin-1. This selective binding plays a crucial role in the axonal cargo transport within the neurons.
Transport via dyneins
Dyneins are minus-end-directed motor proteins. These motors are responsible for carrying out crucial functions within the cell, such as the arrangement of axonal complex microtubule assemblies, signal transduction within the primary cilium, and positioning of Golgi apparatus near the cell center. Among the two dyneins present in the cell, cytoplasmic dynein is primarily responsible for transporting organelles and vesicles. Dynein has two globular heads attached to two stalks and intermediate and light chains that form the upper domain. ATP hydrolysis takes place within the globular heads. The movement of cytoplasmic dynein resembles walking, where one stalk moves ahead, followed by the other. The large cytoplasmic dynein molecule cannot bind directly to the organelles or vesicles; it requires an additional protein called dynactin. Dynactin has a short actin-like filament, Arp1. The Arp-1 domain recognizes and attaches to the receptor domain of the organelles or vesicles. The cytoplasmic dynein and dynactin are activated only after binding with a specific organelle or vesicle, forming a tripartite complex. The tripartite complex then transports the organelles and vesicles.
Suggested Reading
- Mizuno, N., Toba, S., Edamatsu, M., Watai‐Nishii, J., Hirokawa, N., Toyoshima, Y.Y. and Kikkawa, M., 2004. Dynein and kinesin share an overlapping microtubule‐binding site. The EMBO journal, 23(13), pp.2459-2467.
- Kato, Y., Miyakawa, T. and Tanokura, M., 2018. Overview of the mechanism of cytoskeletal motors based on structure. Biophysical reviews, 10(2), pp.571-581.