http://www.biosciencetechnology.com/news/2014/07/scientists-shed-new-light-nerve-cell-growth?
Amidst the astounding complexity of the billions of nerve cells and trillions of synaptic connections in the brain, how do nerve cells decide how far to grow or how many connections to build? How do they coordinate these events within the developing brain?
In a new study, scientists from the Florida campus of The Scripps
Research Institute (TSRI) have shed new light on these complex
processes, showing that a particular protein plays a far more
sophisticated role in neuron development than previously thought.
The study, published in the journal PLOS Genetics, focuses
on the large, intracellular signaling protein RPM-1 that is expressed
in the nervous system. TSRI Assistant Professor Brock Grill and his team
show the surprising degree to which RPM-1 harnesses sophisticated
mechanisms to regulate neuron development.
Specifically, the research sheds light on the role of RPM-1 in the
development of axons or nerve fibers—the elongated projections of nerve
cells that transmit electrical impulses away from the neuron via
synapses. Some axons are quite long; in the sciatic nerve, axons run
from the base of the spine to the big toe.
“Collectively, our recent work offers significant evidence that
RPM-1 coordinates how long an axon grows with construction of synaptic
connections,” said Grill. “Understanding how these two developmental
processes are coordinated at the molecular level is extremely
challenging. We’ve now made significant progress.”
Putting together the pieces
The study describes how RPM-1 regulates the activity of a single
protein known as DLK-1, a protein that regulates neuron development and
plays an essential role in axon regeneration. RPM-1 uses PPM-2, an
enzyme that removes a phosphate group from a protein thereby altering
its function, in combination with ubiquitin ligase activity to directly
inhibit DLK-1.
“Studies on RPM-1 have been critical to understanding how this
conserved family of proteins works,” said Scott T. Baker, the first
author of the study and a member of Grill’s research team. “Because
RPM-1 plays multiple roles during neuronal development, you wouldn’t
want to interfere with it. But exploring the role of PPM-2 in
controlling DLK-1 and axon regeneration could be worthwhile—and could
have implications in neurodegenerative diseases.”
The Grill lab has also explored other aspects of how RPM-1 regulates neuron development. A related study, also published in PLOS Genetics,
shows that RPM-1 functions as a part of a novel pathway to control
beta-catenin activity—this is the first evidence that RPM-1 works in
connection with extracellular signals, such as a family of protein
growth factors known as Wnts, and is part of larger signaling networks
that regulate development. A paper in the journal Neural Development
shows that RPM-1 is localized at both the synapse and the mature axon
tip, evidence that RPM-1 is positioned to potentially coordinate the
construction of synapses with regulation of axon extension and
termination.
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