Well-known Clathrin Protein Reveals New Tricks
Study shows clathrin protein plays a key role in cell division
A protein called "clathrin," which is found in every human cell and plays a critical role in transporting molecules within a cell, also plays a key role in cell division, according to new research at the University of California, San Francisco (UCSF).
The discovery was featured on the cover of the Journal of Cell Biology in August 2012, and sheds light on the process of cell division while providing a new angle for understanding cancer. Without clathrin, cells divide erratically and unevenlya phenomenon that is a hallmark of cancer.
"Clathrin is doing more than we thought it was doing," said Frances Brodsky, research director. Brodsky is a professor in the UCSF Department of Bioengineering and Therapeutic Sciences, a joint department of the Schools of Pharmacy and Medicine. She holds joint appointments in Microbiology and Immunology, as well as Pharmaceutical Chemistry.
Akin to a building block in a child's construction set, clathrin can create large complexes. When quantities of this protein are assembled together, it forms tough cages into which cells pack essential biological moleculeshormones, neurotransmitters, membrane proteins and other payloads to be transported throughout the cell.
Once thought to be solely for transporting
molecular materials within cells,
scientists have uncovered more and more
of clathrin's hidden functions in the last six years.
Several years ago, clathrin was found to play a role in the formation of "spindles." Normally when a cell divides, it forms a spindle by laying down tracks of structural proteins as scaffolds to separate the cell's DNA (the chromosomes) into two equal collectionsone identical set of DNA for each of the new daughter cells. It was found that clathrin stabilizes these spindles.
Brodsky and her colleagues have added another function. When they deleted clathrin from cells using a technique called RNA interference, a technique which involves infusing small genetic fragments into the cell to block the production of clathrin, they were able to see that clathrin is needed to stabilize the centrosomes in dividing cells.
Tagged with fluorescent chemicals and viewed under a microscope, the centrosomes within a cell about to divide looks like two glowing dots. But without clathrin, the dots increase in number.
Brodsky and her colleagues traced this result to a protein complex formed by a component of clathrin called CHC17, which is directly associated with stabilizing the centrosome.
Deleting CHC17 or chemically inactivating it,
led to fragmented centrosomes and abnormal spindles.
This discovery reveals a pathway towards abnormalities
in chromosome segregation associated with cancer.
Frances Brodsky, PhD
The article, "Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG" by Amy B. Foraker, Stéphane M. Camus, Timothy M. Evans, Sophia R. Majeed, Chih-Ying Chen, Sabrina B. Taner, Ivan R. Corrêa Jr., Stephen J. Doxsey and Frances M. Brodsky appears in the August 20, 2012 issue of the Journal of Cell Biology. See: http://dx.doi.org/10.1083/jcb.201205116
In addition to the group at UCSF, authors on this study are affiliated with New England Biolabs, Inc., in Ipswich, MA, and the University of Massachusetts Medical School in Worcester, MA.
Original article: http://jcb.rupress.org/content/198/4/591