Summary: Scientists have mapped the molecular structure of glutamate receptors in the cerebellum for the first time using cryo -electronic microscopy. These receptors are critical for how neurons in the cerebellum communicate, affect movement, balance and cognition.
When visualizing the receptors attached to proteins in synapses, researchers hope to inform future therapies that could restore the function after the lesion or genetic interruption. Although it cannot be translated immediately to treatments, this fundamental discovery offers a road map to repair the brain circuits damaged in motor and cognitive disorders.
Key facts:
First visualization: Cryo-EM revealed the structure of cerebellar glutamate receptors in an almost atomic resolution. Synaptic precision issues: Receptors are organized with demanding spatial precision to detect neurotransmitters signals.
Source: Oregon Health and Science University
For the first time, scientists who use cryo -electronic microscopy have discovered the structure and shape of key receptors that connect neurons in the brain’s cerebellum, which is behind the brainstem and plays a critical role in functions such as coordination of movement, balance and cognition.
The research, published today in the journal Nature, provides a new vision that could lead to the development of therapies to repair these structures when they are interrupted by genetic lesions or mutations that affect motor skills: sitting, standing, walking, running and jumping: learning and memory.
The discovery of the scientists of the Oregon Health & Science University implies an investigation in basic sciences that will not immediately lead to a new pill or treatment, but it is an example of an American commitment to medical research sustained for decades to advance human health.
Published in one of the most prestigious scientific journals in the world, the new research was supported by the National Health Institutes and the Howard Hughes Medical Institute.
The study reveals the organization of a specific type of glutamate receptor, a chemical neurotransmitter that transmits signals between neurons and is considered the primary exciter neurotransmitter in the brain, attached with proteins grouped in synapses or unions, among neurons in the cerebellum.
“Synapse are crucial in all aspects of brain function, but the molecular structure has not been well understood in terms of how these pieces are formed together in a functional synapse,” said principal author Eric Gouaux, Ph.D., the main scientist of the OHSU Vollum Institute.
“It is really essential to have organized receptors in the right place so that they can detect neurotransmitters released by an adjacent cell.”
Examine glutamate in the cerebellum
Using the Crio-Electrons Microscopy of Ohsu, established as one of the three national centers in 2018 and housed in the reinforced basement of a building on the Campus of the University of Waterfront, the researchers examined the form of a particular type of glutamate receptor in the cerebellum of the rodents at an almost atomic scale.
“We know that if there is a genetic injury or mutation in the cerebellum, it can lead to devastating balance, movement or cognition disorders,” said co -author Laurence Trussell, Ph.D., a professor of otolaryngology/head and neck surgery at the Faculty of Medicine of OHSU and scientist at the Vollum Institute.
“This type of glutamate receptor seems to be really important in the way the cerebellum works. It is completely possible that the development of drugs that are directed to these receptors can improve their function.”
Gouaux, a researcher at Howard Hughes Medical Institute and Jennifer and Bernard Lacroute, president endowed in Neuroscience Research in OHSU, said the new discovery could have applications for new treatments.
“We were interested in this question about synapse engineering and molecular vision that can one day help repair damaged synapses,” he said. “This is a new super exciting address with possible therapeutic applications.”
The main author Chengli Fang, Ph.D., postdoctoral researcher in the Gouaux laboratory, did almost all the experiments reported in the publication.
In addition to Gouaux, Trussell and Fang, co -authors include Cathy J. Spangler, Ph.D., Jumi Park, Ph.D., from OHSU; and Natalie Sheldon de Ohsu and the Howard Hughes Medical Institute.
FINANCING: The research reported in this publication was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Cerebrovascular Accident, and the National Institute of Deafness and other communication disorders, all national health institutes, K00CA253730 awards numbers, R01NS038631, R35ns116798 and R01DC004450.
The content is the exclusive responsibility of the authors and does not necessarily represent the official NIH opinions.
On this neuroscience research news
Author: Erik Robinson
Source: Oregon Health and Science University
Contact: Erik Robinson – Oregon Health and Science University
Image: The image is accredited to Neuroscience News
Original research: closed access.
“Update and Group of Noelin of Native CA2+” ampa receptors by Eric Gouaux et al. Nature
Abstract
Grouping and Grouping of Noelin of ampa receptors native Ca2+
The ampa type ionotropic glutamate receptors (Ampar) are an integral part of the rapid excitation synaptic transmission and play a vital role in synaptic plasticity, engine coordination, learning and memory.
While extensive structural studies have been carried out in recombinant ampar and waterproof framing of native calcium (IC) along with its auxiliary proteins, the molecular architecture of the permeable spaces of native calcium (CP) has remained indefinite.
To elucidate the composition of the subunit, physiological architecture and the mechanisms of activation of CP cushions, here we present the first visualization of these receptors, purified immunoafinity of the cerebella of the rat, and solve their structures using cryolectronic microscopy (Cryo-EM).
Our results indicate that the predominant assembly consists of GLUA1 and GLUA4 subunits, with the GLUA4 subunit that occupies the B and D positions, while the auxiliary subunits, including the canvases, are found in the positions B ‘D’ D ‘
In addition, we resolved the structure of the Noelin 1-Glua1/A4 complex, in which Noelin 1 (Noe 1) specifically joins the GLUA4 subunit in positions B and D. In particular, Noe 1 stabilizes the terminal amino domain (ATD) domain without affecting the receptor activation properties.
Noe 1 contributes to the Ampar function through the formation of dimetric-asérica sets that probably participate in extracellular networks, group receptors within synaptic environments and modulate the receptor’s response capacity to synaptic entries.
