Exam 1 Flashcards
Plasma membrane
Surrounds the outside of the cell Composed of a lipid bilayer and proteins Polar heads on outside, non- polar/hydrophobic tails on inside
What types of proteins are associated with the lipid bilayer?
Peripheral and integral membrane proteins
What are the two faces of the plasma membrane? How do you image them?
E-face and P-face Image via freeze fracture technique - pull layers apart, proteins go with layers
Which face of the plasma membrane usually has more integral proteins associated with it?
The P face
E-face
The layer of the plasma membrane backed by the extracellular space
P-face
The layer of the plasma membrane backed by the cytoplasm (protoplasm)
What are the functions of different integral membrane proteins?
Pumps Channels Receptors Linkers Enzymes Structural
What are the different methods of transport across the plasma membrane?
Simple Diffusion Carrier Proteins Channel Proteins
Simple diffusion
Requires no proteins Particles are small and hydrophobic enough to cross the bilayer
Carrier proteins
May be passive (no energy required, usually high to low concentration gradient) or active (energy required, usually ATP) Highly selective
Channel proteins
Ion selective and based on cell needs Regulated by membrane proteins May be voltage-gated
Forms of vesicular transport
Endocytosis (pinocytosis, phagocytosis, receptor-mediated endocytosis) Exocytosis (constitutive, regulated)
Pinocytosis
“Cell drinking” Nonspecific Small proteins and fluid aka clathrin-independent endocytosis
Phagocytosis
Only occurs with specialized cells (i.e. macrophages, neutrophils) - Engulf cell debris and bacteria Requires the rearrangement of the actin cytoskeleton Forms phagosomes aka clathrin-independent, actin-dependent endocytosis
Receptor-mediated endocytosis
Vemicrotubulessicles form when receptors on the surface bind to specific cargo molecules Formation of endocytic vesicles may involve pitting of the membrane (clathrin helps form pit) - Cell membrane invaginates, forms a vesicle, and the vesicle travels along - uncoat vesicle when cargo inside is ready to be unloaded Formation of endocytic vesicles may be clathrin dependent or independent
Endosomes
Generally the end point of vesicular important May be early endosomes or late endosomes, although they eventually may become lysosomes As they mature, they become more acidic within the lumen
Early endosomes
Sort and recycle proteins pH 6.2-6.5 (slightly acidic, close to neutral)
Late endosomes
Pre-lysosomes pH around 5.5 (more acidic) Late endosomes fuse with lysosomes for degradation of lumenal content
Lysosomes
Degrade proteins/molecules from endocytic pathways and autophagy Very acidic - pH around 4.7 Digestive organelles with tough membranes that resist digestion - Contain a diverse array of acid hydrolases that become active when the lumen reaches a pH of 5 Lysosomal membrane proteins include lysosome-associted membrane proteins, glycoproteins, and other integral membrane proteins
What are the four pathways that lead to intracellular digestion in lysosomes?
Receptor-mediated endocytosis Pinocytosis Phagocytosis Autophagy
Proteasomes
Large nonmembranous cytoplasmic or nuclear protein complexes that are capable of degrading single polypeptides and proteins
Lysosomal Storage disorders
Deficiency in one or more lysosomal enzymes, leading to accumulation of substrate in the lysosome, which cause a cell to malfunction and eventually die Tay-Sachs disease I-cell disease Niemann-Pick disease (type A) Gaucher disease - Also includes the mucopolysaccharideoses, which result in deficiency in enzymes that degrade glycosaminoglycans, leading to accumulation of partially degraded glycosaminoglycans that, over time, leads to thickening of the tissue and compromised cell and organ function
Tay-Sachs disease
Lysosomal storage disorder characterized by: - loss of vision and hearing - muscle atrophy due to loss of nervous tissue - early death (often by age 5) - deficiency is in hexoaminidase - substrate that accumulates is GM2 ganglioside in neurons
I-cell disease
Lysosomal storage disorder characterized by: - skeletal abnormalities - hepatomegaly - mental retardation due to abnormal cellular architecture - early death (often by age 8) - deficiency is in N-acetylglucosaminyl-1-phosphotransferase - this leads to lysosomal hydrolases being secreted instead of being phosphorylated in the Golgi
Niemann-Pick disease (type A)
Lysosomal storage disorder characterized by: - hepatosplenomegaly - neurodegeneration - progressive wasting due to sphingomyelin accumulation in all cells of body - early death (often by 3 years) - deficiency is in sphingomyelase - sphingomyelin accumulates
Gaucher disease
Lysosomal storage disease which affects the spleen, liver, lungs, and bone marrow due to accumulation of glucosylceramide in cells of the macrophage-monocyte system - deficiency is in Beta-glucocerebrosidase - accumulation of glucosylceramide
Peroxisomes
Single membrane proteins synthesized on cytoplasmic ribosomes - Contain catalase and other peroxidases (which break down hydrogen peroxide) - Abundant in kidney and liver cells Involved in: -Beta-oxidation of fatty acids - detoxification of ethanol - synthesis of plasmalogens, which maintain membrane integrity, especially in CNS
Zellweger Syndrome
Inability to import proteins to peroxisomes, leading to accumulation of long-chain fatty acids - plasmalogen synthesis is compromised - results from a mutation in a gene incoding the integral membrane protein Pex2 - nonfunctional peroxisomes, CNS demyelination, early death
Types of Exocytosis
Constitutive
Regulated
Constitutive Endocytosis
Proteins are secreted when they are made
i.e. antibodies
Regulated Endocytosis
Product is made and stored in vesicles
Proteins secreted when signaled
i.e. Endocrine and exocrine cells, neurons: hormones and neurotransmitters
Trafficking of Secreted proteins
Proteins that are 1) secreted, 2) will become integral membrane proteins, or 3) will be membrane-bound/part of an organelle, are synthesized on the rough ER ribosomes and then trafficked to the proper location based on a signal sequence within the polypeptide chain
Alpha 1 antitrypsin deficiency
A single amino acid substitution renders the rER unable to export alpha-1 antitrypsin (A1AT)
- this leads to decreased activity of A1AT in the blood and lungs and abnormal deposition of defective A1AT within the rER of liver hepatocytes, resolting in emphysema (COPD) and impaired liver function
Rough Endoplasmic Reticulum
Continuous with nuclear envelope
Contains Ribosomes
Involved in Synthesis of Secreted and membrane proteins
Highly developed in secretory Cells - i.e. osteoblasts and glandular cells
Ribosomes
Composed of proteins and ribosomal RNA
They may be free in the cytoplasm or membrane-bound to the rough ER
- they play an essential role in protein synthesis
- Stain basophilic
Smooth Endoplasmic Reticulum
No ribosomes
Tubular in appearance
Tubular in appearance
Abundant in cells that function in:
- lipid metabolism
- detoxification
- steroid synthesis
In skeletal muscle, it is referred to as the sarcoplasmic reticulum (SR) and it plays a major role in Ca++ storage
In response to drugs (including ethanol), hepatocytes will greatly increase the amount of sER in the cell
Stains acidophilic
Golgi Apparatus
Functions in post-translational modification, sorting, and packaging of proteins
- typically found close to the nucleus
- consists of flattened sacs of cisternae along with small vesicles and larger vacuoles
- Modifications include addition and trimming of sugar moieties and sulfation
- Packaged proteins may be secreted, become a part of the plasma membrane (integral membrane proteins), or be shipped to an organelle (such as a lysosome)
The cis Golgi Network is closest to the nucleus, the trans Golgi network is furthest from the nucleus
Mitochondria
The “powerhouses” of the cell
Function in generation of energy (ATP) via oxidative phosphorylation, tricarboxylic acid cycle, Beta-oxidation of fatty acids
- Derived from prokaryotic cells - have own (circular) DNA, division and replication do not follow that of the cell cycle for the cell they are located in
2 membranes, 2 compartments
Not present in red blood cells or terminal kartinocytes
- many in oxidative skeletal muscle fibers
Nonliving inclusions
Secretory granules
Stored energy (e.g. glycogen and fat)
Pigments (e.g. hemoglobin and melanin)
Crystals (e.g. those in Sertoli and Leydig cells)
Inclusions typically contain products of metbolic activity
What types of particles make up the cytoskeleton?
Microtubules (involved in transportation and movement)
Actin (involved in membrane structure and motility)
Intermediate filaments (involved in mechanical strength)
Structure of Microtubules
Gamma-tubulin ring
Alpha and beta tubulin molecules (which bind GTP/GDP)
Growing (+) and non-growing (-) ends
Dynamic instability is used to describe microtubules as they are constantly remodeling
Functions of Microtubules
Vesicular Transport
Movement of Cilia and Flagella
Alignment, separation of chromosomes during cell division
What motor proteins aid in transport along microtubules?
Kinesins (towards the plus end, out to the membrane)
Dyneins (towards the minus end, in towards the MTOC/nucleus)
Centrosomes
Function in aligning the mitotic spindle during cell division
Basal bodies, an assembly of cilia and flagella, are found at the base
-Microtubules composing the centrosomes extend from the basal bodies
Centrioles
Composed of 9 sets of microtubule triplets
Central point of MTOC (Microtubule organizing center) assumbly
Short, drum-like appearance
When 2 centrioles are paired at 90 degrees from each other, it is called a centrosome
Kartagener’s syndrome
Dysfunction of microtubules
Leads to immobilization of cilia, infertility
How is chemotherapy related to microtubules?
Many chemotherapy treatments prevnt microtubules from working properly, thus preventing cell division
i. e. taxol prevents depolymerization, which is necessary during mitosis for choromsome to separate (cell gets stuck in metaphase)
- Vinblastine and vincristine inhibit the formation of the mitotic spindle in cell division
Assembly of Actin
Spontaneously assemble, dissassemble
Requires energy (ATP)
Actin binding proteins help stabilize actin filaments as they form, help to send them in the proper direction
Flexible (thinner than microtubules)
Directionality - plus end (where actin is added on) and minus end (where actin depolymerizes)
Functions of actin filaments
Cell shape/structure
Microvilli
Anchorage and movement
Extension of cell processes
Locomotion
Phalloidin
Compound found in some poisonous mushrooms
Prevents depolymerization by binding to F-Actin
Cytochalasin B and D
Prevents polymerization
Inhibits lymphocyte migration, phagocytosis, cell division
Intermediate filaments
Differe from microtubules and actin in that it has no monomers that polymerize or depolymerize
- Static structure (does not form and reform)
Plays a structural role in Cell-cell and cell-matrix junctions
Classes of Intermediate filaments: Keratins, Vimentins, Neurofilaments, Lamins
Keratins
A class of intermediate filaments found in all epithelial cells
Vimentins
A class of intermediate filaments found in fibroblasts and neurons
Neurofilaments
A class of intermediate filaments found in neurons
Lamins
A class of intermediate filaments found in most differentiated cells and all nucleated cells
- this is the class of intermediate filament found in the nucleus, not the cytoplasm
Alcoholic Liver cirrhosis
Accumulation of keratins (intermediate filaments)
Formation of Mallory bodies (intracellular lesions)
Alzheimer’s disease
Involves accumulation of neurofilaments, which form neurofibrillary tangles
The Nucleus
A membrane-limited compartment that contains the genome (genetic information) in eukaryotic cells
Contains - nuclear envelope, nuclear lamina, chromatin (heterochromatin and euchromatin), nucleolus
The nuclear envelope
Two bilayer membranes with a perinuclear space in between
Perinuclear space is continuous with the endoplasmic reticulum
During cell division the nuclear envelope breaks up
Nuclear lamina
Scaffolding for the chromosomes and the nuclear pores in the nucleus
Cross-hatch look to it - made of intermediate filaments
A type of cytoskeleton that helps keep chromatin organized so it’s not floating around in the nucleus
Exists right underneath the nuclear envelope
What are some diseases related to impaired nuclear lamina architecture?
Progeria (lamin A/C)
Emery-Dreifuss muscular dystrophy (EDMD; lamins, lamin receptors, emerin)
Heterochromatin
More condensed chromatin that stains darker
Not transcriptionally active
Euchromatin
Lighter staining chromatin, less condensed
Transcriptionally active
Nuclear pore complex
Allows for transport into and out of the nucleus
During mitosis, the nuclear envelope disappears
Nucleolus
Structure inside nucleus that functions in rRNA synthesis, ribosome assembly
More prominent in cells that are active in protein synthesis
Functions in regulation of the cell cycle - Nuclepstemin-p53 binding protein
Target of viruses - alter cell cycle to control viral replication
Progeria
Premature aging, typically live to mid to late teens
Disruption in lamins (intermediate filaments in nuclear lamina) including Lamin A/C
Chromatin
A combination of DNA and structural proteins packaged to fit into the nucleus
Heterochromatin is tightly packed
Euchromatin is less packed and transcriptionally active
What chromosomes are made of
Chromosomes
Composed of condensed chromatin
Consists of 2 chromatids connected by a centromere
Visible during metaphase, mitosis only (interphase, chromatin is generally not condensed)
Two ends are telomeres, which shorten with each cell division
Telomerase
Enzyme which repeatedly adds nucleotide sequences to the telomere end
Role in oncogenesis (formation of malignant cells)
Barr Body
In individuals with two X chromosomes, one X chromosome is repressed and stays tightly condensed
This is often found adjacent to the nuclear envelope
Nucleostemin
A protein regulates the cell cycle and influences cell differentiation
May play a role in malignancy
Types of cell renewal
Static: no longer divide (CNS, cardiac muscle)
Stable: divide as necessary (smooth muscle and endothelial cells)
Slow renewing: fibroblasts, epithelial cells of the eye lens
Fast renewing: blood cells, epithelial cells
Phases of the cell cycle
M-phase: mitosis
Interphase:
- G1 - Gap 1 (proteins needed for DNA synthesis)
- S (DNA synthesis)
G2 - Gap 2 (growth and reorganization, accumulation of energy for division)
G0 phase
GTD - terminal differentiation
Mitotic Catastrophe
Malfunction of any of the DNA damage checkpoints of the spindle assembly checkpoint in early mitosis
Failure to arrest the cell cycle before or at mitosis results in abberrant chromosome segregation (i.e. aneuploidy, tumor cell development)
A malfunction at which cell cycle checkpoint may result in malignant transformation?
G1 restriction checkpoint
What checkpoints exist in G1?
G1 DNA Damage checkpoint
G1 restriction checkpoint (right before it moves into S phase)
What cell cycle checkpoints exist in S phase?
S DNA damage checkpoint
What cell cycle checkpoints exist in G2 phase?
Unreplicated DNA checkpoint
G2 DNA damage checkpoint
What cell cycle regulatory checkpoints exist in M phase?
Spindle-assembly checkpoint
Chromosome-segregation checkpoint
Cell Cycle Regulation is accomplished by which proteins?
Two protein complexes
Cyclin
Cyclikn-dependent kinase
These are checkpoint regulators
Different complexes act at different stages of the cell cycle
Some cancer treatments may target cyclin and/or cyclin dependent inase that is affected in cancerous growth