Study is the first to show that lowering the levels of lipid in nerve terminals affects the efficiency of neurotransmission

Yale researchers demonstrate the crucial role of a membrane lipid called phosphatidylinositol-4,5-bisphosphate (PtdIns (4,5)P2) in the communication of information between synapses in the brain, according to a study published this week in Nature.

"This study is the first to show that lowering the levels of this lipid in nerve terminals affects the efficiency of neurotransmission," said senior author, Pietro De Camilli, Eugene Higgins Professor of Cell Biology and a Howard Hughes Medical Institute investigator.

De Camilli's laboratory has extensively studied the mechanism underlying cycling of synaptic vesicles, the small sacs containing neurotransmitters that exchange information between neurons. Synaptic vesicles release their contents at junctions between nerve terminals by fusing with the plasma membrane where they rapidly re-internalize, reload with neurotransmitter, and are reused.

The researchers genetically engineered laboratory mice lacking the enzyme PIPK1-gamma at the synapse. This enzyme plays a major role in the synthesis of PtdIns(4,5)P2, a member of a class of lipids called phosphoinositides. The mice born without PIPK1-gamma were apparently normal, but they were unable to feed and died quickly. Studies of their nervous system revealed lower levels of PtdIns(4,5)P2 and a partial impairment both of the process of fusion of synaptic vesicles as well as of their recycling.

De Camilli said these studies provide new insight into basic mechanisms in synaptic transmission, but also have implications for medicine. For example, Down syndrome patients have an extra copy of the gene encoding the enzyme synaptojanin 1, which degrades PtdIns (4,5)P2 in the brain. Patients with Lowe syndrome, who also have mental retardation, lack another PtdIns(4,5)P2 degrading enzyme. Cancer and diabetes also can result from abnormal metabolism of phosphoinositides, De Camilli said.

"Typically, studies of synaptic transmission have focused on membrane proteins," said De Camilli. "Only recently has the importance of the chemistry of membrane lipids and of their metabolism started to be fully appreciated. The field is still in its infancy, but rapid advancements in the methodology for the analysis of lipids promise major progress in the field and the possibility of identifying new targets for therapeutic interventions in human diseases."

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Understanding behavioral changes in early dementia