Balancing brain chemistry. Scientists in Paul Greengard’s laboratory have discovered a protein that plays a
central role in integrating several major molecular signaling pathways in
the brain’s striatum, a region that controls movement and balance.
Disruption of these pathways is associated with several diseases of the
nervous system, including Huntington’s and Parkinson’s. The new
protein, called regulator of calcium signaling (RCS), binds to another
protein known as calmodulin, thereby inhibiting its activity. Calmodulin
mediates the actions of calcium within cells, which are essential for cell
signaling. The researchers found that, through its interaction with
calmodulin, RCS mediates the balance between the neurotransmitters
acetylcholine and dopamine. The finding opens the door to new therapies.
Greengard is the university’s Vincent Astor Professor and head of the
Laboratory of Molecular and Cellular Neuroscience.
Fluid dynamics. The
human respiratory tract is lined with cells that have cilia — tiny
hair-like projections that sweep mucus up and out of the lungs. People with
a genetic mutation that cripples these cilia cannot clear the mucus and
suffer chronic infections. They also sometimes develop hydrocephalus, an
accumulation of fluid in the brain. New research from Rockefeller’s Nathaniel Heintz, Ines
Ibanez-Tallon, with assistance from the Bio-Imaging Resource Center
directed by Alison North, and German colleagues, explains the connection.
In experiments with mice, they showed for the first time that, as in the
respiratory system, there are cilia-studded cells that line the walls of
fluid-filled cavities in the brain called ventricles and push fluid along
in the proper direction. A mutation in the mouse gene Mdnah5, analogous to
the human counterpart, cripples cilia in these brain cells as well as in
respiratory cells. As a result, these mice develop hydrocephalus. Heintz is
head of the Laboratory of Molecular Biology.
Human Molecular Genetics, September 15, 2004
Chromosomal end game. Mammalian chromosomes end in long stretches of repeated DNA
sequences known as telomeres. These telomeres, in turn, terminate in loops
that protect the DNA from damage. Now scientists in Titia de Lange’s
laboratory have found that telomeres can be shortened dramatically and
quickly by losing loop-sized stretches of DNA in a process called
homologous recombination. The culprit is a mutant form of the TRF2 protein.
In its normal form, TRF2 protects telomere loops, but a mutant called TRF2deltaB, in combination with other proteins, induces the large DNA
deletions. The researchers propose that losing loops may be a normal part
of the way cells regulate telomere length, one that could be harnessed in
the treatment of certain cancers. de Lange is Leon Hess Professor and head
of the Laboratory of Cell Biology and Genetics.
Cell, October 29, 2004
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