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

5. Similarities and Differences

6. Form a plaque

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

18. Localize when interact

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

42. Transmembrane proteins

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

45. Interact homphylically

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

59. Cardiac cells functioning

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

63. Transmembrane proteins

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

74. Heterotypic binding

75. Tissue specific as well

76. Two different types of heteromeric GJ connect with one another

77. Heterotypic binding

78. Tissue specific as well

79. Two of the same type of homomeric or heteromeric GJ connect with one another

80. Homotypic Binding

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

95. Uncontrolled mitosis

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

114. Skin/epithelia = carcinomas

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

119. Nervous system cancers

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

147. Disorganized cytoskeleton