#nucleoporins

[bpod-bpod]

Overcompensating

Like a large business needs an internal communications team and efficient post room to keep everything working smoothly together, cells require systems to keep departments in tune. Nucleoporins are proteins that ferry essential messages from the nucleus (the cell’s HQ) to other areas, but mutations linked to these can play a role in cancer development. To understand why, researchers examined protein production in fruit fly wings (pictured, nucleoporins labelled green) when certain nucleoporins are disabled. Without them, cell cycles were disrupted, and both cell death and cell replication increased. The extra proliferation of material compensates for the cell death, but if nucleoporin failures coincide with other mutations that block cell death, unrestricted growth occurs and cancers arise. This revealed that nucleoporin mutations change protein synthesis, which impacts cell signalling to cause compensatory growth, and can, in combination with other factors, cause cancer, highlighting them as a potential target for future treatments.

Written by Anthony Lewis

Image from work by Ajai J. Pulianmackal and colleagues

Molecular Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Image on cover of Disease Models & Mechanisms, March 2022

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[currentsinbiology]

Scientists Map the Portal to the Cell’s Nucleus 

Like an island nation, the nucleus of a cell has a transportation problem. Evolution has enclosed it with a double membrane, the nuclear envelope, which protects DNA but also cuts it off from the rest of the cell. Nature's solution is a massive -- by molecular standards -- cylindrical configuration known as the nuclear pore complex, through which imports and exports travel, connecting the bulk of the cell with its headquarters.

In research described March 14 in Nature, scientists at Rockefeller University and their colleagues have delineated the architecture of the nuclear pore complex in yeast cells. The biological blueprint they uncovered shares principles sometimes seen on a much larger scale in concrete, steel, and wire.

"It reminds us of a suspension bridge, in which a combination of sturdy and flexible parts produce a stress-resilient structure," says Michael P. Rout, who led the work together with Brian T. Chait.

The pore complex contains 552 component proteins, called nucleoporins, and scientists hadn't previously known how they all fit together. It took a combination of approaches to assemble a comprehensive map of these pieces. The researchers hope this new molecular structure will enable new studies of how the nuclear portal functions normally, and how defects in it lead to diseases such as cancer.

Seung Joong Kim, Javier Fernandez-Martinez, Ilona Nudelman, Yi Shi, Wenzhu Zhang, Barak Raveh, Thurston Herricks, Brian D. Slaughter, Joanna A. Hogan, Paula Upla, Ilan E. Chemmama, Riccardo Pellarin, Ignacia Echeverria, Manjunatha Shivaraju, Azraa S. Chaudhury, Junjie Wang, Rosemary Williams, Jay R. Unruh, Charles H. Greenberg, Erica Y. Jacobs, Zhiheng Yu, M. Jason de la Cruz, Roxana Mironska, David L. Stokes, John D. Aitchison, Martin F. Jarrold, Jennifer L. Gerton, Steven J. Ludtke, Christopher W. Akey, Brian T. Chait, Andrej Sali, Michael P. Rout. Integrative structure and functional anatomy of a nuclear pore complex. Nature, 2018; DOI: 10.1038/nature26003

[phil-iannaccone]

Traffic Control

February 21st, 2014

We have seen how a cell makes proteins, but to be of any use and to perform their assigned functions proteins have to get from the ribosome to where they are needed.  This process is called protein trafficking. Some proteins need to be in the membrane, some need to be exported out of the cell, some need to be in the nucleus, some in the mitochondria, some need to make energy at just the right time and place. Without a mechanism to regulate where the newly synthesized proteins go chaos would reign and the cell would die. It would be like having the girders that support a building dumped in the lobby, or the natural gas that heats your house pumped into the bathroom instead of into the furnace.

How is the traffic controlled? Special signals that facilitate interaction with transporters of many different types are built into the protein. For example there is a nuclear localization signal that allows a protein to stick to a structure called a nuclear pore, which looks like a life saver candy embedded in the nuclear envelope (the surrounding membrane of the nucleus). The nuclear pore is made up of perhaps 30 different proteins called nucleoporins.

Camillo Golgi, the discoverer of the Golgi apparatus won a Nobel Prize in 1906.

Proteins that need to go into the nucleus have special sequences of about 7 amino acids that stick to a protein called importin (because it imports its cargo protein, also it is importint!) and moves the protein into the nucleus. These special signals work like zip codes and facilitate the movement of proteins to the correct location. In some cases the proteins move; in which case they are said to be translocated, in combination with a specialized transporter called a chaperone (importin is an example of one chaperone). This movement can occur as the protein is being made or afterwards.

The endoplasmic reticulum (blue) receives proteins as they are made from ribosomes (red).  Vesicles pinch off from the endoplasmic reticulum with protein attached and follow microtubule tracks to the Golgi apparatus (salmon).  After processing in the Golgi apparatus the proteins once again become cargo in vesicles that pinch off.  When the protein is to be released from the cell those vesicles fuse with the outer membrane of the cell and release their cargo.  On the right is a very high magnification of a Golgi apparatus. Download for free at http://cnx.org/contents/7d5ecac2-a4c4-4167-b952-c3a9bde54252@5.

The microtubule track is the blue green rod at the bottom.  The large green spheres are vesicles with protein cargo. The sphere is carried along the track by motors called kinesin, the red and blue leg like structures.  In a process that requires energy the legs walk along the track carrying their vesicle cargo!

Image courtesy of BioMEDIA ASSOCIATES, LLC

http://en.wikipedia.org/wiki/Kinesin

There is a great deal of controversy over how the proteins move through the Golgi apparatus and two main mechanisms are currently in favor, one is called “Kiss and Run”! But the proteins that need to do make their way through this structure and are then thought to wind up in a new sphere, this time pinched off from the membranes of the Golgi. These are called exocytic vesicles (exocytic because they will dump their “cargo” outside of the cell). These exocytic vesicles fuse with the plasma membrane (the membrane surrounding the cell) by sticking to special proteins called SNAREs and the protein is released to the outside.

This transport highway is a two-way street and proteins made by other cells can get inside by sticking to the plasma membrane on structures called receptors.  They are pinched off into spheres containing the proteins called endocytic vesicles (endocytic meaning "inside the cell"). Some of these can fuse with the Golgi apparatus and are further processed in many ways. The proteins can be directed to the part of the cell that needs them. In some cases they can be broken down into component parts in a kind of cellular recycling plant for proteins that ensures the right amount of a protein is around. All of this action occurs in all of our cells thousands and thousands of times each second!

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.