4.23.2010
- 1. Desmosomes
- 2. Like hemidesmosomes because they involved the formation of plaques on the cytoplasmic side of membrane and link/organize keratans or intermediate filaments
- 3. Difference: different types of transmembrane proteins interacting with one another in a homophylic way to link the PM together
- 4. Hemidesmomsomes use integrins to link to the basal lamina
- 7. Organize keratan intermiedate filaments
- 8. Desomosomes link up cells together
- 9. Hemi link cell membrane to basal lamina
- 10. There are two types of transmembrane proteins that form desmosomes
- 11. Desmocollin
- 12. Desmoglein
- 13. Characeteristics
- 14. Interact homophylicily on EX side
- 15. Within cadherin family of protein
- 16. Bind in a homophylic, Ca2+ dependant way
- 17. Interact with in the same type of association with opposing proteins on opposite cell membrane
- 19. Serve as attachment sites for proteins that can link desmosome to keratan
- 20. There are proteins that link desmosomes proteins to keratan
- 21. Plakoglobin
- 22. Globular protein that only associates with cytoplasmic region of desmoglein or desmocolin
- 23. Bound by globular region of dimeric protein desmoplakin
- 24. Desmoplakin
- 25. Directly associates with the keratan flaments/intermediate filaments and organizes them on these lateral sides of the PM
- 26. Keratan filaments are then organized at these sites where plaques are formed as desmosomes assemble between cells
- 27. Create attachments sites/a network for organizing the keratin that will provide structural support for epithelial cells as they form tissue (as well as hemidesmosomes)
- 28. Epithelial cells are mucosal linings, lung linings as well
- 29. Tight Junctions
- 30. Fairly weak associations actually
- 31. Require lots of TJs formed in a particular way
- 32. Make a meshwork near the apical side of the cell
- 33. Form a separation between apical and basal side of the cell <<< important
- 34. Initial studies done to find proteins involved and how important TJs are
- 35. Labeled solutions added to basal or apical side
- 36. Does the solution diffuse?
- 37. When you mutate a protein, what happens in diffusion?
- 38. Two types of proteins make up tight junctions
- 39. Claudin
- 40. Occludin
- 41. Charactersistics
- 43. Each have 4 transmembrane spanning doains
- 44. Interact with each other on EXC side of PM by linking EXC loops between the trasmembrane domains
- 46. Claudin binds with claudin
- 47. Occludin binds with occludin
- 48. Function
- 49. On apical side
- 50. Active mechanism of transport to bring in glucose after food has been digested into epithelial cells
- 51. Requires the function of Na/Glucose transporter
- 52. High levels of glucose in lumen brought in, in a regulated way
- 53. Glucose diffuses through cell cytoplasm
- 54. Through passive transporter, glucose transporter, into EXC fluid and through blood capillaries to tissues
- 55. Without TJs glucose would rapidly diffuse through EXC fluid into blood capillaries in an unrestricted way
- 56. Allows epithelial cells to regulate uptake of glucose and bring in as much as is needed at a particular time
- 57. Gap Junctions
- 58. Important in linking cells into cytoplasmic sinsishunt
- 60. Open junctions before contraction
- 61. Ions that drive contraction move through rapidly, linking cytoplasms of all cells making one big cell so that they can contract at the same time and make heart function properly
- 62. Allow small small small molecules to go thorugh such as ions
- 64. Made up of 6 individual GJ polypeptides (connexins) that span the lipid membrane
- 65. There are 14 different genes that are known to encode GJ proteins
- 66. Different combination of the proteins in different tissues
- 67. Homomeric
- 68. Made of the same homomeric proteins
- 69. Heteromeric
- 70. Made of different gap junction proteins
- 71. How the two PM come together
- 72. Two similar types of GJ coming together as PM are joined
- 73. Two different types of homomeric GJ connect with one another
- 75. Tissue specific as well
- 76. Two different types of heteromeric GJ connect with one another
- 78. Tissue specific as well
- 79. Two of the same type of homomeric or heteromeric GJ connect with one another
- 81. Structure of GJs
- 82. Connexins are the individual proteins
- 83. Assembled GJ with 6 connexins is called a connexon
- 84. Open like a shutter when slid together to form a pore
- 85. --------------------END LECTURE ON ECM-------------------------
- 86. CANCER
- 87. Cancer Cells
- 88. Tumors
- 89. All tumors are not cancerous
- 90. Neoplastic cells
- 91. Moles
- 92. Not cancerous
- 93. Cells are benign and remain intact in primary tissue from which they rose
- 94. Divided in an unrestricted way for a period of time
- 96. All cancers have tumoregenic cells but not all tumors are cancerous
- 97. Characteristics of cancer cells
- 98. Reproduce without restrictions on mitosis
- 99. Can invade and colonize regions in and outside of primary source (invasive and colonize)
- 100. Benign
- 101. Neoplastic cells that divide in an unrestricted way but remain in source tissue
- 102. Don’t have to mecome malignant necessarily, form metasteses (1/1000 cells that has become neoplastic can become metastatic
- 103. Can form a tumor, often clonal – arising from a SINGLE cell, which most cancers are often from
- 104. If undergone a mutation, benign cells can loose dependence on attachment to one another as well as to the basal lamina and actively secrete proteases that chew away basal lamina and connective tissue/proteoglycans in connective tissue to move into blood stream and through it.
- 105. Malignant
- 106. Have the ability to migrate to a secondary source
- 107. Can form metastastes/metastasize in secondary site
- 108. Cells attach to endothelium and secrete proteases that allow them to move into tissues of secondary source – extravazation, the same sort of mechanisms that immune cells use to move to another point from the capillaries
- 109. Metastatic
- 110. Tumor in a secondary site that is formed by original malignant cells
- 111. Cues that increase chance of secondary tumor formation in particular cell types
- 112. Ex: Epithelial tumors often lead to liver tumors
- 113. Names given to particular tumor types/types of cancers
- 115. Sarcomas = muscle tissue/connective tissue
- 116. Leukemia/lymphoma = hematopoietic system
- 117. Leukemia – unrestricted growth of t cells or b cells/WBC of immune system
- 118. Gives rise to RBC/WBC/platelets
- 120. Neuromas
- 121. Astrocytomas
- 122. Gliomas
- 123. What makes cells oncogenic/neoplastic? (oncogenic transformation)
- 124. Characteristics
- 125. Normal cells when grown in culture exhibit contact inhibition unless reached hayflick limit
- 126. Cancer cells do not stop dividing. Exhibit a loss of contact inhibition (will grow on top rather than on substrate = loss of contact dependence on ECM/cell adhesion for survival)
- 127. No signal that is mediated to tell a cell to stop dividing
- 128. Don’t depend on adhesions to survive whether to neighbor or substrate
- 129. Lack of dependence on GFs – in regulating mitosis -G1-
- 130. Tumorigenic cells will move through G1 checkpoint, completely independent of it
- 131. Rb Pi’ed > E2F is turned on > past G1 to S phase > DNA divides > Mitosis
- 132. Cells in the presence of GFs will move to senescence and cell growth will stop
- 133. Cancer cells don’t depend on GFs and as time continues, the number of cancer cells increases in a linear way. Loss of senescence (aging and death) in cancer cells
- 134. Disorganized cytoskeleton of mobile cells and not responding to environmental cues.
- 135. MT organization is very dense and doesn’t take on a particular arrangement
- 136. Can form adhesions and break rapidly
- 137. Sometimes arise from any abnormal number of chromosomes (46 for humans) = aneuploidy – (alignment of chromosomes not occurring could be one – or replicative events didn’t occur properly)
- 138. Chemical carcinogens
- 139. Within coding region for p53
- 140. Losing control of p53, cells have a difficult time undergoing apoptosis
- 141. Other sites of DNA
- 142. UV – Cytoseine to two thymidine – disrupts how gene functions
- 143. Tanning beds are UVa and UVb which are more mutagenic than just UV
- 144. Making immortalized cell lines
- 145. Mice cells undergo crisis and proliferate in culture to form an immortalized cell line that is cancerous – dividing in unrestricted way
- 146. Unless virally infected or DNA mutated, human cells won’t become immortalized