Transcript Document

Paul Cullen’s Lectures for BIO402/502
Office hours: Friday 2PM or by appointment
[email protected]
Section II Protein Secretion, Trafficking & Degradation; Signal Transduction; Cytoskeleton & Cell Motility;
ExtracellularMatrix & Cell-Cell Interactions
Dr. Cullen (12 lectures, September 25th - October 23rd)
Protein Delivery to the ER, Golgi, Exocytosis
(Cullen; 1 lect, Sept. 25th ) CHAPTER 12 Alberts
Protein Glycosylation and unfolding
(Cullen; 1 lect, Sept. 30th ) CHAPTER 13 Alberts
Golgi, Snares, COPs and Arfs
(Cullen; 1 lect. Oct. 2th )
CHAPTER 13 Alberts
th
PI Signaling and Vesicle Identity
(Cullen; 1 lect, Oct. 5 )
CHAPTER 13 Alberts
Protein Targeting: Peroxisome/Mitochondria
(Cullen; 1 lect, Oct. 7th )
CHAPTER 12 Alberts
Cell Polarity - Actin Cytoskeleton
(Cullen; 1 lect, Oct. 9th )
CHAPTER 16 Alberts
th
Cell Polarity - Microtubules
(Cullen; 1 lect, Oct. 12 )
CHAPTER 16 Alberts
Origins of Cell Adhesion
(Cullen; 1 lect, Oct. 14th )
CHAPTER 19 Alberts
Cell Adhesion Molecules, Integrins and Mucins
(Cullen; 1 lect, Oct. 16th )
CHAPTER 19 Alberts
The Extracellular Matrix
(Cullen; 1 lect, Oct. 19th )
CHAPTER 19 Alberts
st
Cell Polarity Regulation and Signal Transduction
(Cullen; 1 lect, Oct. 21 )
CHAPTER 15 Alberts
rd
Genomics Approaches to Cell Biology
(Cullen; 1 lect, Oct. 23 )
HANDOUTS
Exam 2 (Proctor: Berezney, October, 29st)
Test will be on October 29th 7PM-9PM
Short answer, medium answer, and essay.
Primarily from the lectures, with the book as a backup.
Exocytosis: Delivery of Secretiory Vesicles to the Cell Suface
Retrograde Transport: Delivery of Vesicles to Internal Compartments
HIV enters through membrane fusion
Influenza enters through receptor-mediated endocytosis
IM-like
Proteins
Hydrophobic
Tails exposed
Snare-like
Phagocytosis
Specialized form of receptor-mediated endocytosis
Macrophages (white blood cells)
Food (in microorganisms), dead cells (1011 red blood cells/day), glass,
Latex beads, asbestos fibers, and antigens, but not other live cells
Temporal Order of Clathrin-Mediated Endocytic Intermediates
Recruitment of Clathrin
Membrane
Membrane Restriction/Fission
Assembly Factors
Curvature
Vesicle Release
PIPK-g
AP-2*
Hip1R*
Amphiphysin2* Dynamin*
AP180A,B*
Epsin*
Endophilin
Actin
Eps15
polymerization
Clathrin
PI(4,5)P2
PI(4,5)P2-binding Proteins*
Conner and Schmid, Nature 2003
Transcytosis from the Basolateral membrane To the Apical
Membrane Allows passage of materials Across cellular boundaries
Antibodies must also transverse the intestine of the infant
neutral
acidic
Figure 12-6 Molecular Biology of the Cell (© Garland Science 2008)
Figure 12-21a Molecular Biology of the Cell (© Garland Science 2008)
Some Proteins made in the mito.
The Mitochondrial Import Sequence is an amphipathic alpha helix
Figure 12-22 Molecular Biology of the Cell (© Garland Science 2008)
TOM = cytosolic proteins to the intermembrane space
TIM = cytosolic proteins to the matrix and inner membrane
OXA = mitochondrially produced proteins to the intermembrane space
Figure 12-23 Molecular Biology of the Cell (© Garland Science 2008)
An in vitro experiment to determine how mitochondrial transport occurs
Figure 12-24 Molecular Biology of the Cell (© Garland Science 2008)
Cytosolic chaperones like Hsp70 keep proteins
Unfolded until they are fed into the mitochondria
And they contribute to the import process.
Figure 12-25 Molecular Biology of the Cell (© Garland Science 2008)
The RTG Network: a signaling pathway from the mitochondria to the
Nucleus.
Mitochondrial retrograde signaling is a pathway
of communication from mitochondria to the
nucleus under normal and pathophysiological
conditions. The best understood of such
pathways is retrograde signaling in the budding
yeast Saccharomyces cerevisiae. It involves
multiple factors that sense and transmit
mitochondrial signals to effect changes in
nuclear gene expression; these changes lead to
a reconfiguration of metabolism to accommodate
cells to defects in mitochondria. Analysis of
regulatory factors has provided us with a
mechanistic view of regulation of retrograde
signaling. Here we review advances in the yeast
retrograde signaling pathway and highlight its
regulatory factors and regulatory mechanisms,
its physiological functions, and its connection to
nutrient sensing, TOR signaling, and aging.
Aging, the greatest disease of all!
Like many young scientists with a novel idea, Kenyon encountered more skepticism than support in the
early 1990s. Indeed, one fellow scientist, worried that she had gone “over the edge,” warned that if she
continued to insist that aging was subject to genetic regulation, she would soon fall off the Earth altogether.
But her world turned out to be round, not flat. And now firmly anchored as, if not exactly the “queen of aging
research,” then certainly its ace, Kenyon commands no fewer than 386,000 entries on a standard Google
search.
The story is now well-known. One of Kenyon’s lab rotation students —
Ramon Tabtiang — in one of his very first experiments, picked a needle
out of the haystack that is the C. elegans genome. In short, he found a
mutant gene, dubbed daf-2, that made worms live twice as long.
http://www.ucsf.edu/science-cafe/conversations/kenyon/