Lecture

Proteomic Applications in Neuroscience: Targeting Cortical Neurons

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Description

This lecture discusses the application of proteomics in neuroscience, focusing on the analysis of cortical neurons and their interactions with striatal neurons. The instructor begins by outlining the classes of proteomic experiments, including expression proteomics, which profiles total protein composition across different conditions. The challenges of classical proteomics, which often leads to a loss of tissue structure resolution, are highlighted. The lecture introduces innovative genetic-based methods for targeting specific cell types, such as cortical neurons, using techniques like APEX and TurboID. A detailed example is presented, showcasing a study that engineered cortical neurons to express APEX peroxidase, allowing for selective biotinylation of proteins in these neurons. This method enables the analysis of cortical neuron proteomes and phosphoproteomes at various developmental stages, revealing key proteins and kinases involved in axon growth and branching. The findings emphasize the importance of targeted proteomics in understanding the complex interactions within the nervous system.

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Related concepts (32)

Proteomics

Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In addition, other kinds of proteins include antibodies that protect an organism from infection, and hormones that send important signals throughout the body. The proteome is the entire set of proteins produced or modified by an organism or system.

Kinase

In biochemistry, a kinase (ˈkaɪneɪs,ˈkɪneɪs,-eɪz) is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group (producing a dephosphorylated substrate and the high energy molecule of ATP).

Axon guidance

Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they manage to find their way so accurately is an area of ongoing research. Axon growth takes place from a region called the growth cone and reaching the axon target is accomplished with relatively few guidance molecules. Growth cone receptors respond to the guidance cues.

Gene expression profiling

In the field of molecular biology, gene expression profiling is the measurement of the activity (the expression) of thousands of genes at once, to create a global picture of cellular function. These profiles can, for example, distinguish between cells that are actively dividing, or show how the cells react to a particular treatment. Many experiments of this sort measure an entire genome simultaneously, that is, every gene present in a particular cell. Several transcriptomics technologies can be used to generate the necessary data to analyse.

Protein kinase

A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase.

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