Jonathan Lytton

Professor

Department of Biochemistry & Molecular Biology

Member

Libin Cardiovascular Institute of Alberta

Cell Signalling and Structure

Ph.D. (Doctor of Philosophy)


Contact information

Location


Research and teaching

Research Activities

The broad subject of investigation in the Lytton laboratory is the control of calcium homeostasis. Calcium ion is a ubiquitous second messenger whose cytoplasmic concentration regulates a host of diverse biological events including muscle contraction, neurotransmitter secretion, hormone signaling, vesicle targeting and cell cycle control. We study proteins that transport calcium across membranes using molecular, biochemical, cellular and physiological techniques to understand structure, function and regulation.

A major area of focus concerns a family of K-dependent Na/Ca-exchangers (NCKX) that are abundant in brain neurons, but also expressed selectively in other tissues. The unique roles these exchangers play in physiology is being pursued using recombinant structure-function studies, cell biological analyses, and genetically engineered mice. Our work is currently focused on two of these transporters, NCKX2 and NCKX4. The former appears to play a role in hippocampal plasticity underlying motor learning and working memory consolidation. The latter appears to play a pivotal role in the normal function of brain circuits underlying feeding behaviour and satiety. Current efforts are directed toward understanding the mechanisms that lead from exchanger function to the regulation of these important physiological processes.

 

Fig.1. HEK293 cells expressing the rat brain K-dependent Na/Ca-exchanger, NCKX2, are analyzed using a calcium-sensitive fluorescent indicator dye.

 

Fig.2. Localization of NCKX2 (in red) in mouse brain (top left), and in hippocampus with various markers (in green): NMDA-receptor-1 (NR1; top right is enlarged from the other NR1 panel), glial fibrillary associated protein (GFAP), glutamic acid decarboxylase (GAD65), synapsin-1 (SN1), microtubule-associated protein-2 (MAP2), neurofilamin (NF).

 

Fig.3. NCKX4 knockout mice are thinner than their wild type littermates (A). Hypothalamic PVN neurons are activated in NCKX4 KO mice (B). Hypothalamic neurons respond to MSH with Ca signals (C).

Research Areas: 

Cell Signalling and Structure

Research Personnel: 

  • Sunita Sharma, MSc. Senior Research Technician
  • Stephanie Thibodeau, Laboratory Technician
  • Mohamed Hassan, Graduate Student
  • Maryam Al-Khannaq, Graduate Student
  • Leslie McGill, Administrative Assistant

 


Publications

PubMed