SC430 Molecular Cell Biology Welcome to Unit 6 Seminar with Dr Hall-Pogar Tonight we will discuss –Biological processes in the cell –Diseases that result from errors in the cell Cystic fibrosis –I will be available at AIM:KaplanHallPogar before and throughout the seminar if you have any questions or issues. We will begin promptly at 9:00pmEST

2 Unit Review DB Project –Part I: Protein Synthesis –Part II: Protein Mutations

3 Overview Cell membrane separates living cell from nonliving surroundings –thin barrier = 8nm thick Controls traffic in & out of the cell –selectively permeable –allows some substances to cross more easily than others hydrophobic vs hydrophilic Made of phospholipids, proteins & other macromolecules

4 inside cell outside cell lipid salt aa H2OH2O sugar NH 3 What molecules can NOT get through directly? –polar molecules H 2 O –ions salts, ammonia –large molecules starches, proteins Diffusion through phospholipid bilayer What molecules CAN get through directly? –fats & other lipids

5 Getting through cell membrane Passive Transport –Simple diffusion diffusion of nonpolar, hydrophobic molecules –lipids –high  low concentration gradient –Facilitated transport diffusion of polar, hydrophilic molecules through a protein channel –high  low concentration gradient Active transport –diffusion against concentration gradient low  high –uses a protein pump –requires ATP

6 Transport summary simple diffusion facilitated diffusion active transport ATP

7 Cystic Fibrosis CF causes the body to produce an abnormally thick, sticky mucus on epithelial surfaces. A genetic disease affecting approximately 30,000 children and adults in the United States. It is one of the most common lethal inherited disorders among caucasians In 1997, the median survival age for males with CF was 32.7 years versus 28.9 years in females One in 31 Americans (one in 28 Caucasians) - more than 10 million people - is an unknowing, symptom-less heterozygous carrier of the defective gene Source: Cystic Fibrosis Foundation

8 CF Mutations and Transport How do the various CF mutations affect the function of CFTR proteins? The various mutations (>1,300) that have been shown to cause CF have been categorized into four classes –Class I mutations cause defective protein production with a total loss of functional CFTRs –One defect produces a truncated CFTR due to premature stop mutants.

9 CFTR Cystic fibrosis transmembrane conductance regulator (CFTR) –Protein that in humans is encoded by the CFTR gene –ABC transporter class ion channel that transports chloride and thiocyanate ions across cell membranes –Mutations of the CFTR gene affect functioning of the chloride ion channels in these cell membranes, leading to CF and congenital absence of the vas deferens

. Goodman B E, Percy W H Advan in Physiol Edu 2005;29:75-82 ©2005 by American Physiological Society

. Goodman B E, Percy W H Advan in Physiol Edu 2005;29:75-82 ©2005 by American Physiological Society

12 Seminar Question? Give another example of transport gone wrong

13 Cell signaling: responding to the outside world Cells interact with their environment by interpreting extracellular signals via proteins that span their plasma membrane called receptors Receptors are comprised of extracellular and intracellular domains The extracellular domain relays information about the outside world to the intracellular domain The intracellular domain then interacts with other intracellular signaling proteins These intracellular signaling proteins further relay the message to one or more effector proteins Effector proteins mediate the appropriate response

14 Cell to Cell Communication Juxtacrine signaling - with each other via direct contactJuxtacrine signaling Paracrine signaling - over short distancesParacrine signaling Endocrine signaling - over large distancesEndocrine signaling Some cell-to-cell communication requires direct cell-cell contact cells form gap junctionscell-cell contactgap junctions