Lis1 regulates dynein by sterically blocking its mechanochemical cycle
Katerina Toropova1, Sirui Zou2, Anthony J Roberts2
1Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
Elife
|November 8, 2014
Summary
Lis1 protein regulates cytoplasmic dynein (motor protein) by blocking its mechanical cycle, keeping it attached to microtubules. This mechanism is crucial for cell division and intracellular transport.
Area of Science:
- Molecular Motor Function
- Cellular Biology
- Structural Biology
Background:
- Cytoplasmic dynein (motor protein) regulation is vital for eukaryotic cell functions.
- Lis1 protein is a known dynein regulator, but its mechanism of action was unclear.
- Dynein's role in cell division, intracellular transport, and brain development highlights the importance of its regulation.
Purpose of the Study:
- To elucidate the mechanism by which Lis1 regulates dynein's microtubule binding.
- To understand how Lis1 controls dynein's motor activity.
Main Methods:
- Three-dimensional electron microscopy to determine complex structure.
- Single-molecule imaging and biophysical assays.
- In vivo functional assays.
Main Results:
- Structural analysis revealed Lis1 binding to dynein's AAA+ ring sterically hinders the 'linker' element.
- Shortening the linker to bypass Lis1 abolished Lis1-mediated regulation in single-molecule experiments.
- Lis1 directly blocks the progression of dynein's mechanochemical cycle.
Conclusions:
- Lis1 maintains dynein's persistent microtubule-bound state by physically obstructing its motor cycle.
- This provides a mechanistic understanding of Lis1's role in dynein regulation.
- Findings are critical for understanding dynein-dependent processes in eukaryotes.
Related Concept Videos
01:05Mechanism of Ciliary Motion
6.0K
The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
6.0K
01:32Microtubule Associated Motor Proteins
11.9K
Eukaryotic cells have different motor proteins for transporting various cargo within the cell. These motor proteins differ based on the filament they associate with, the direction they move within the cell, and the type of cargo they transport. Motor proteins that associate with microtubules are known as microtubule-associated motor proteins. There are two families of microtubule-associated motor proteins —Kinesins and Dyneins. Both these proteins assist in the transport of cellular...
11.9K
01:43The Movement of Organelles and Vesicles
7.5K
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,...
7.5K
01:31Mechanism of Lamellipodia Formation
4.1K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
4.1K
01:39Mechanism of Filopodia Formation
3.5K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
3.5K
01:45Destabilization of Microtubules
3.9K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
3.9K