L7: Cell Biology VI

Question 1

What are MAPs?

Answer 1

• Microtubule-associated proteins

- Function to stabilize microtubules

Question 2

Clinical relevance of MAPs

Answer 2

• Tau is an example of a microtubule-associated protein
• In Alzheimer’s disease, the amount and type of tau is modified and the microtubule binding affinity is lost. Consequently, tau pairs accumulate in the cytoplasm of the neuron impairing its function

Question 3

Structure of microfilaments

Answer 3

• Comprised of subunits of actin

Question 4

What inhibits polymerization of actin?

Answer 4

• Cytochalasin B

Question 5

Staining of actin

Answer 5

• Phallacidin conjugated with green fluorescein dye

Question 6

Functions of microfilaments

Answer 6

1. ) Structural support (cell cortical fibers)
2. ) Forms core of microvilli and sterocilia
3. ) Movement (muscle contracts, cell migration, short-range transport of organelles)
4. ) Cytokinesis
5. ) Formation of filopodia and lamelipodia

Question 7

Structure of thick filaments

Answer 7

• Myosin

Question 8

Mutation in gene for myosin causes what?

Answer 8

• Severe form of cardiomyopathy

Question 9

Structure of intermediate filaments

Answer 9

Composed of various molecules depending on tissue:

1. ) Cytokeratin
2. ) Desmin
3. ) Vimentin
4. ) Neurofilaments
5. ) Glial fibrillary acidic proteins
6. ) Nuclear lamins

Question 10

Where is cytokeratin found?

Answer 10

• Found in epithelial cells

Question 11

Clinical relevance of cytokeratin

Answer 11

• Mallory bodies seen in alcoholic liver disease
• Epidermolysis bullosa simplex: mutations in keratin 5 or 14 gene prevents keratin from assembling into strong networks. Epidermis of skins becomes fragile and is easily damaged.

Question 12

What type of intermediate filament constitutes the Mallory body?

Answer 12

• cytokeratin

Question 13

Where is desmin found?

Answer 13

• Found in striated muscle and non-vascular smooth muscle

Question 14

Clinical relevance of desmin

Answer 14

• Mutations in desmin are involved in cardiac and skeletal myopathies

Question 15

Where is vimentin found?

Answer 15

• Many mesodermal tissues including Fibroblasts and Chondroblasts

Question 16

Where are neurofilaments found?

Answer 16

• Type of intermediate filament found in most nerve cells

Question 17

Clinical relevance of neurofilaments?

Answer 17

• Mutations are associated with neuropathies

Question 18

Where are GFAPs found?

Answer 18

• Glial fibrillary acidic proteins are found in astrocytes

Question 19

Clinical relevance of GFAP

Answer 19

• Aggregates of GFAP known as Rosenthal’s fibers are demonstrated in Alexander disease (a degenerative disease of white brain matter), chronic gliosis and astrocytomas

Question 20

What are Rosenthal’s fibers?

Answer 20

• Aggregates of GFAP and other proteins characteristic of pilocytic astrocytoma

Question 21

Where is nuclear lamin found?

Answer 21

• Nuclei of all cells

Question 22

Function of intermediate filaments

Answer 22

• Structural support

Question 23

Clinical relevance of knowing intermediate filament types

Answer 23

• Analysis of neoplastic cells for intermediate filament type allows pathologist to determine type of tumor

Question 24

Discuss structure and function of centrosome and centrioles

Answer 24

• Centrosome (aka MTOC: microtubule-organizing center) are specialized cytoplasmic regions near nuclei containing two centrioles (which are organelles) and amorphous pericentriolar material. MTOC is a conductor of microtubule: number, polarity, direction, orientation, organization)
• Centrioles oriented perpendicular to one another, comprised of microtubules in 9 x 3 arrangement. Centrioles replicated to form procentrioles which in turn become basal bodies required to form microtubules associated with cilia and flagella
• Function: form mitotic spindle in mitosis

Question 25

Is the nucleus basophilic or acidophilic?

Answer 25

• Basophilic d/t presence of negatively charged phosphate groups on nucleic acids

Question 26

What does shape of nucleus say?

Answer 26

• Can help identify cell type
• Also used to classify neoplasms along spectrum. Well-differentiated are typically benign, where non-differentiated is a hallmark typically of malignancy

Question 27

List structures of nucleus

Answer 27

• Nuclear envelope
• Nuclear (fibrous) lamina
• Nuclear matrix (nucleoplasm)
• Chromatin
• Nuclear bodies

Question 28

List and describe the function nuclear bodies (domains)

Answer 28

1. ) Nucleolus
2. ) Cajal bodies: modifying and assemblying molecular machinery to splice pre-mRNA to mRNA. Molecules here include snRNA, snoRNA, snRNPs.
3. ) GEMs (Gemini of Cajal bodies): resemble Cajal bodies, may not be distinct. Proposed function is same as Cajal bodies
4. ) Interchromatin granule clusters (speckles): represent storage depots of snRNAs and proteins. These molecules are released into karyoplasm and become engaged in pre-mRNA splicing.
5. ) Promyelocytic leukemia bodies (PML): involved in modifying and assemblying proteins tasked with DNA repair and triggering apoptosis. May also engage in repression of transcription and protect against certain viruses.
6. ) Polymorphic interphase karyosomal association (PIKA). Elusive function, proposed that these bodies are involved in promoting transcription of snRNA.

Question 29

What is spinal muscular atrophy?

Answer 29

• Fatal disorder characterized by muscle wasting
• Mutation of SMN (survival of motor neurons) gene encodes a defective SMN protein that is localized to the GEMs. Normal protein functions in snRNA production. When defective, death of motor neurons in anterior gray horns of spinal cord results.

Question 30

Structures of nuclear envelope

Answer 30

1. ) Bilayer membrane
2. ) Perinuclear space
3. ) Nuclear pores penetrating bilayer

Question 31

Distinguish between the inner and outer nuclear membranes

Answer 31

Outer:
- Studded with ribosomes, which synthesize proteins located on outer membrane, inner membrane or within perinuclear space. This is continuous with rER
Inner:
- closely associated with nuclear lamina

Question 32

Describe selective/non-selective transport through nuclear pores

Answer 32

• Pores are freely permeable to molecules and ions with diameter less than 9 nm
• Selective transport of: RNAs, ribosomal subunits, proteins and other larger (greater than 9 nm) molecules and ions
• Transports occurs in an energy-dependent GTP manner with Ran, importin, exportin proteins

Question 33

Describe structure of nuclear lamina

Answer 33

• Specialized region of the nuclear matrix composed of three classes of polypeptides called lamins that are closely associated with the inner nuclear membrane

Question 34

Functions of nuclear lamina

Answer 34

• Support of inner membrane
• Phosphorylation of lamins causes disassembly of the nuclear envelope during prometaphase of mitosis
• Dephosphorylation of lamins causes reassembly of the nuclear envelope during telophase of mitosis

Question 35

Clinical relevance of lamins

Answer 35

• Mutations associated with cardiomyopathy

- Two forms of progeria, a disease that rapidly accelerates aging

Question 36

What is chromatin?

Answer 36

• DNA coiled around basic histones. Basic structural unit of chromatin is the nucleosome, which has 4 pairs of histone proteins.

Question 37

Two forms of chromatin

Answer 37

a. ) Heterochromatin: condensed, coiled, transcriptionally inactive chromatin
b. ) Euchromatin: decondensed, uncoiled, transcriptionally active chromatin

Question 38

42 yo female presents with mass in her neck. She complains of difficulty breathing and swallowing. PEX reveals palpable, firm, nontendern nodule in thyroid gland area. Lab studies show elevations of thyroxine and triiodothyronine in blood. Biopsy of thyroid gland obtained and sent to path. The pt is diagnosed with papillary thyroid cancer. What histologic features informed the diagnosis?

Answer 38

• Orphan Annie eye nuclei, which refer to clear nuclei