Summers

Neurobiology

text: Principles of Neural Science - Kandel, Schwartz and Jessell: Read pages 88-103 for this lecture end

X. Cell type determines what mRNA is expressed 	back to IX. Action Potential


	A. Brain cells transcribe more DNA than any other tissue


		1. ~200,000 mRNA sequences (10-20X more than liver or kidney)


		2. due to greater variety and number of cells


			a. 1011 nerve cells (100 billion)


		3. each expresses more genetic information than other types of cell


			b. increased synthesis increases possible communication, which 
			   is the function of the nervous system            


XI.  Neural Proteins

	A. protein structure =  polymer of amino acids (polypeptide) 


		1. N-terminal end has a free amino group (NH2)


			a. translation at the ribosome begins at the N-terminal 


		2. C-terminal 

			a. carboxyl group (COOH    or     

	B. Cytosolic Proteins


		1. Fibrillar elements of the cytoskeleton


			a. neurofilaments, tubulins, actins


				i. moved to and used in dendrites and axons


		2. Enzymes


			a. eg. choline acetyltransferase (synthesizes ACh) 


		3. Few, if any, cotranslational or posttranslational modifications or processing


			a. N-acetylation, N-myristoylation, phosphorylation


	C. Nuclear, Mitochondrial and Peroxisomal Proteins


		1. posttranslational importation into organelle


			a. presequences - determine distribution


				i. N-terminal sequences recognized by receptors


	D. Membrane and Secretory Proteins


		1. formed on ribosomes of the endoplasmic recticulum (rER)		

		
				a. begins on free ribosomes


		2. N-terminal portion = signal sequence 


			a. binds to Signal Recognition Particle (SRP)


				i. arrests translation


			b. SRP binds to receptor on cytoplasmic surface ER = Docking Protein  


				i. displaces SRP & translation begins again


			c. peptide transported through ER membrane signal sequence usually
			   cleaved from mature protein by cisternal signal peptidase


 				i. ATP + foldases or chaperonins required for transfer


				ii. peptide grows at C-terminal end


			d. Cotranslational Transfer continues until Halt or Stop Transfer segment is
			   reached in the peptide


				i. discarded signal sequence fixes protein position in membrane


					(1) protein may span multiple times and extend beyond the
					    membrane at the N- or C-terminals


				ii. complete transfer results in a secretory protein (eg. transmitter)


					(1) secretory products under go sequential and specific processing
					    by proteolytic enzymes in the ER lumen, Golgi, Vesicles, etc.


						(a) may contain more than one active peptide


					(2) glycosylation etc. may also occur ( may anchor peptide)


XII. Axonal Transport
						


	A. Fast Anterograde (forward: cell body to axon terminal)


		1. most all newly synthesized membranous organelles


			a. secretory proteins are packaged at golgi into synaptic vesicles


		2. ~ 400 mm/ day, saltatory motion


		3. depends on oxidative metabolism, but is independent of the cell body


		4. utilizes filaments of the cytoskeleton


			a. microtubules provide stationary track


				i. microtubule ATPases:Kinesin (perhaps like muscles)	
				
				
	B. Slow Axonal


		1. cytoplasm is move by axioplasmic flow


			a. also proteins which make up cytoskeleton


		2. ~ 0.2 mm/ day


	C. Fast Retrograde			


		1. returns materials from terminals to cell bodies


			a. for degredation or restoration and reuse


			b. informs the soma of events at distal axon processes (eg. NGF)


		2. membrane-bound (part of lysosomal system) - endocytosis


		3. move along microtubles; half as fast as anterograde


		4. motor molecule = Dynein (also an ATPase)


	D. Secretory products are released from the axon terminal, into
	    the synaptic cleft, by exocytosis, and products or metabolites
		are recovered from the synapse by endocytosis

XIII. Synapses

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