Mass spectrometry-based characterization of cell-to-cell signaling molecules in the nervous system

mass spectrometry;neuropeptide;signaling molecules;peptidomics;structure elucidation

Yang, Ning

关键词: mass spectrometry;    neuropeptide;    signaling molecules;    peptidomics;    structure elucidation;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/95541/YANG-DISSERTATION-2016.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Cell-to-cell signaling molecules are an important class of endogenous molecules which are responsible for cell-to-cell communication within organisms. Small molecules and peptides work as neurotransmitters and neuromodulators in the nervous system and play important regulatory roles in a wide range of physiological events and animal behaviors, such as pain sensation, food intake, memory, circadian rhythm, tissue regeneration and drug addiction. Cell-to-cell signaling molecules are highly diverse in structure or sequence and their quantities are different at various time points or locations in the nervous system. In addition, cell-to-cell signaling molecules are usually expressed in relatively low abundance level in cells. All these features make the characterization of cell-to-cell signaling molecules a challenging task.Multiple methods have been successfully applied to study cell-to-cell signaling molecules in different animal models. Mass spectrometry (MS), with the assistance of improved sampling and separation techniques, can reveal identity and structure of cell-to-cell signaling molecules and also provide insight into their changes in different biological processes. Various sample types are used in the study of cell-to-cell signaling molecules, such as cell releasates, tissues and biological fluids. This often requires an optimized use of an MS platform or a combination of them, depending on the practical situation and research goal. In this dissertation, four different MS platforms which cover both electrospray ionization (ESI) and matrix assisted laser desorption/ionization (MALDI) were used to characterize cell-to-cell signaling molecules secreted by or contained in animal models of rotifers, mice and rats in both a targeted and untargeted manner. For targeted studies, a separation protocol or detection channel is established and optimized specifically for one or a few molecules of interest, whose functions or involvements in certain biological processes are known. For untargeted studies, MS is usually coupled with bioinformatics for peptide identification or integrated with statistics for comparative quantitation. Findings from these studies help facilitate our understanding of cell-to-cell communications in different animal models. In addition, the work presented in this dissertation also includes development of novel analytical methods and evaluation of different sampling methods, which represent a contribution in the aspect of methodology.