L7: Cell Biology VI Flashcards
What are MAPs?
- Microtubule-associated proteins
- Function to stabilize microtubules
Clinical relevance of MAPs
- 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
Structure of microfilaments
- Comprised of subunits of actin
What inhibits polymerization of actin?
- Cytochalasin B
Staining of actin
- Phallacidin conjugated with green fluorescein dye
Functions of microfilaments
- ) Structural support (cell cortical fibers)
- ) Forms core of microvilli and sterocilia
- ) Movement (muscle contracts, cell migration, short-range transport of organelles)
- ) Cytokinesis
- ) Formation of filopodia and lamelipodia
Structure of thick filaments
- Myosin
Mutation in gene for myosin causes what?
- Severe form of cardiomyopathy
Structure of intermediate filaments
Composed of various molecules depending on tissue:
- ) Cytokeratin
- ) Desmin
- ) Vimentin
- ) Neurofilaments
- ) Glial fibrillary acidic proteins
- ) Nuclear lamins
Where is cytokeratin found?
- Found in epithelial cells
Clinical relevance of cytokeratin
- 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.
What type of intermediate filament constitutes the Mallory body?
- cytokeratin
Where is desmin found?
- Found in striated muscle and non-vascular smooth muscle
Clinical relevance of desmin
- Mutations in desmin are involved in cardiac and skeletal myopathies
Where is vimentin found?
- Many mesodermal tissues including Fibroblasts and Chondroblasts
Where are neurofilaments found?
- Type of intermediate filament found in most nerve cells
Clinical relevance of neurofilaments?
- Mutations are associated with neuropathies
Where are GFAPs found?
- Glial fibrillary acidic proteins are found in astrocytes
Clinical relevance of GFAP
- Aggregates of GFAP known as Rosenthal’s fibers are demonstrated in Alexander disease (a degenerative disease of white brain matter), chronic gliosis and astrocytomas
What are Rosenthal’s fibers?
- Aggregates of GFAP and other proteins characteristic of pilocytic astrocytoma
Where is nuclear lamin found?
- Nuclei of all cells
Function of intermediate filaments
- Structural support
Clinical relevance of knowing intermediate filament types
- Analysis of neoplastic cells for intermediate filament type allows pathologist to determine type of tumor
Discuss structure and function of centrosome and centrioles
- 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
Is the nucleus basophilic or acidophilic?
- Basophilic d/t presence of negatively charged phosphate groups on nucleic acids
What does shape of nucleus say?
- 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
List structures of nucleus
- Nuclear envelope
- Nuclear (fibrous) lamina
- Nuclear matrix (nucleoplasm)
- Chromatin
- Nuclear bodies
List and describe the function nuclear bodies (domains)
- ) Nucleolus
- ) Cajal bodies: modifying and assemblying molecular machinery to splice pre-mRNA to mRNA. Molecules here include snRNA, snoRNA, snRNPs.
- ) GEMs (Gemini of Cajal bodies): resemble Cajal bodies, may not be distinct. Proposed function is same as Cajal bodies
- ) Interchromatin granule clusters (speckles): represent storage depots of snRNAs and proteins. These molecules are released into karyoplasm and become engaged in pre-mRNA splicing.
- ) 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.
- ) Polymorphic interphase karyosomal association (PIKA). Elusive function, proposed that these bodies are involved in promoting transcription of snRNA.
What is spinal muscular atrophy?
- 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.
Structures of nuclear envelope
- ) Bilayer membrane
- ) Perinuclear space
- ) Nuclear pores penetrating bilayer
Distinguish between the inner and outer nuclear membranes
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
Describe selective/non-selective transport through nuclear pores
- 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
Describe structure of nuclear lamina
- Specialized region of the nuclear matrix composed of three classes of polypeptides called lamins that are closely associated with the inner nuclear membrane
Functions of nuclear lamina
- 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
Clinical relevance of lamins
- Mutations associated with cardiomyopathy
- Two forms of progeria, a disease that rapidly accelerates aging
What is chromatin?
- DNA coiled around basic histones. Basic structural unit of chromatin is the nucleosome, which has 4 pairs of histone proteins.
Two forms of chromatin
a. ) Heterochromatin: condensed, coiled, transcriptionally inactive chromatin
b. ) Euchromatin: decondensed, uncoiled, transcriptionally active chromatin
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?
- Orphan Annie eye nuclei, which refer to clear nuclei
