Stabilizing force for good communication between neurons & muscle cells found

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Stabilizing force for good communication between neurons and muscle

cells found

http://www.eurekalert.org/pub_releases/2008-10/mcog-sff100908.php

You can't raise a finger without your brain directing muscle cells,

and scientists have figured out another reason that usually works so

well.

A neuron sends a message, or neurotransmitter, to the muscle cell to

tell it what to do. To get the message, the receiving cell must have

a receptor. Oddly, the unstable protein rapsyn is responsible for

anchoring the receptor so it's properly positioned to catch the

message.

Medical College of Georgia scientists have found what keeps rapsyn in

proper conformation.

It is a heat shock protein, one of a large family of molecular

chaperones that make sure proteins get where they are needed and do

what they should, says Dr. Lin Mei, chief of developmental

neurobiology at MCG and Georgia Research Alliance Eminent Scholar in

Neuroscience.

Hsp90â helps stabilize rapysn so receptors can get and stay where

needed, according to research published in the Oct. 9 issue of

Neuron. Dr. Mei suspects that other hsp siblings have a similar

caretaker role in neuron-to-neuron communication in the brain.

Scientists knew rapsyn's role in getting neuromuscular receptors to

aggregate and stay where needed, but they didn't know what stabilized

it. " It makes you wonder how to control this naughty boy which is

very important, " says Dr. Mei, the study's corresponding author.

They found hsp90â wherever rapsyn clustered in muscle cells. When

they disrupted its activity or expression, they realized hsp90â's

stabilizing role in forming and maintaining receptor clusters, says

Dr. Shiwen Luo, postdoctoral fellow in Dr. Mei's lab and the study's

first author. Rapsyn and the receptor apparently interact, then

hsp90â comes along to help stabilize the relationship.

Rapsyn mutations have been implicated in muscular dystrophies

including congenital myasthenia gravis. MCG researchers are looking

now to see if a mutated rapsyn still interacts with hsp90â.

They used a type of acetylcholine nicotinic receptor at the

neuromuscular junction as a model for their studies of brain

development and communication. The junction is 1,000 times larger

than connections, or synapses, between two neurons but structurally

similar. Fundamentals include presynaptic terminals that release

neurotransmitters picked up by receptors on the postsynaptic side.

Terminals and receptors must be lined up well, whether it's a muscle

cell or neuron getting the message. " In central nervous system

synapses and at the neuromuscular junction, receptors have to be

concentrated at the right spot to receive the neurotransmitter

released, " says Dr. Mei. If receptors are in the wrong place, the

message can be weak or even lost.

At the neuromuscular juncture, communication is usually

straightforward, with primarily one neurotransmitter and one

principal receptor. " Whenever you tell a muscle to move, it moves. If

you want your muscles to think, you wouldn't be able to pick up a

pin, " says Dr. Mei. In the brain, where neurons have thousands of

synapses, it's more of a negotiation. " Signals have to be integrated

in the neuron for it to decide what to do. "