Okay, the second part is the synthesis and trafficking of neuronal proteins. The synthesis of neuronal proteins is most like the protein synthesis in other cells, so most of protein are synthesized in the cell body and dendrites. And now there are some reports showing in the axon region there are local proteins synthesized, but it's not fully confirmed. So now we say that the major protein synthesis happens in the cell body and the dendrites. So the information for synthesis as a protein is encoded in DNA within the nucleus. The DNA will be transcribed into mRNA, and then this process is regulated by some DNA binding proteins transcription factors. And then these are transcription factor synthesize in the cytosol and can go into nucleus to regulate to the gene expression of these proteins. So our brain express large amounts of proteins. So these protein, these mRNA transcripts are 10 or 20 times more than the transcripts in they kidney or our liver, so from here, we can see our brain is very active from this transcription point of view. So in the mature neurons, the chromosome no longer duplicates and the function only in gene expression, so our neurons cannot divide anymore. So the only function for chromosome here in neurons Is to express genes and then make proteins. So the chromosome in neurons exists in a relative uncoiled state in our neurons. Besides nuclear DNAs in neurons. As similar to other cells, there are some circular mitochondria DNAs. These mitochondria DNAs synthesis decode some mitochondria proteins. The synthesis of all the protein starts in the cytosol region. So let's go back to Cell Biology 101, so protein translation and synthesis. So this is our ribosome, the is the mRNA. So mRNA chain get into the ribosome. The ribosome start the translation of protein, of peptide chains, so the amino acid will add to the peptide chain. The peptide chain after synthesized, the peptide chain will be cleaved off the ribosome. So this picture is the cell body where the protein gets synthesized in the neuron and this is the axon. So if we blow up this small part here, we get into this big picture. The upper part here is the nucleus. This is nuclear pore. The mRNA get out from nuclear pore into the cytosol area. So in the neurons the protein synthesis can happen in either cytosol region or ER, Membrane, rough ER Membrane. The fate or the location of proteins eventually are determined by where the protein are synthesized. So the protein that synthesized in the cytosol region will be located at either cytosol, membrane or mitochondria. The protein gets synthesized on the ER membrane or transmembrane protein or secreted protein So the protein synthesized in the cytosol. There are nuclear, peroxisomal, and mitochondrial protein encoded by cell nucleus are synthesized in the cytosol region. And import from the nucleus, through the nuclear pores after a folding not involved transport through a membrane. The cytosol and the nucleoplasm are theoretically continuous. So the cytosol and the nucleolus, although there are nucleopore between the two parts, so they are theoretically connected to each other. So, the mitochondrial and peroxisomal proteins reach their native conformation only after import into the target organelles. And then the movement of this chain, this polypeptide chain through the bilayer of the mitochondrial membrane requires chaperone proteins. They're not get there by themselves, but they need a chaperon protein, the help of the chaperon proteins. So the second part is the proteins synthesised in the rough ER. So first part of these proteins are secretory proteins. The protein will be secreted outside of the cell. We call it secretory proteins. Normally these proteins have signal peptides, signal sequence, and then this signal sequence can be cleaved after they are processed. And the other part of this ER synthesized protein is the transmembrane protein in the vacuolar apparatus or on the plasma membrane. So for these transmembrane proteins, we need a signal region for transmembrane domain and normally it's hydrophobic stop-transfer segment. And then these proteins in the nervous system, they're very important proteins for these at this category is neurotransmitter receptors as we just mentioned and NR2B and NMDA receptor. NMDA is a neurotransmitter receptors for glutamate, and ion channels as were mentioned, a sodium channels, potassium channels. And also there are another category of proteins called GPI anchored proteins, so these proteins, the full length protein are outside of the cell. They attach to the membranes through an anchor called a GPI anchor protein. So these are the proteins synthesized in the ribosome at the ER. so the polypeptide chain get elongated, and then eventually cleaved from the ER, the protein secreted outside of the cell. Or if the polypeptide chain has a transmembrane domain, the protein chain, or peptide chain, will stop at this transmembrane domain and will further processed in Golgi apparatus, and then sometime the proteins will get onto the plasma membrane. A GPI-anchored protein, So one famous GPI-anchored protein, this is this GPI anchor, and then one famous GPI-anchored protein is prion protein. So this is Stanley Prosner, and then this is Prosner standing in the Nobel Prize lecture in 1997. This is his famous prion protein. The prion protein has two conformations. One is enriched with alpha helix, and then the other with beta sheets, so we can call this alpha helix-enrich protein a good prion. This protein is expressed, highly expressed, in almost all our cell types in our body. And then if this good prion turn, somehow turn into this beta sheet rich confirmation this bad prion, then this protein become pathogenic and it's the particle, it's the solely particle responsible for scrapie disease, mad cow disease, and in human CJD.