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Editor’s Corner

Autophagy—the crossword puzzle

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ABSTRACT

It’s April, so it is time to lighten up (think April Fools’ Day). In this issue of the journal, I have two different sets of puzzles for you. Of course, these are not just for your amusement; there is an educational component as well. For example, the crossword puzzle requires you to think about autophagy and perhaps do some searching for names or terms that you are less familiar with (the Guidelines is always a good source of information in this regard). In addition, the crossword puzzle uses official HGNC nomenclature unless otherwise specified – another learning opportunity. Note that this is an alphabet-only puzzle, so dashes, spaces and numbers are omitted. Thus, the clue “The C. elegans homolog of ULK1” would have the answer “UNC”. The second challenge is directly nomenclature based. The goal in this case is to identify as many nomenclature errors as you can in the puncta published in this issue. So, have fun, learn, impress your colleagues and take a break from lab work; unless you are working in my lab – in that case, you should be working at the bench or writing a paper (you know I don’t go for this kind of tomfoolery).

Across

2. Mutations in this protein lead to cholesterol accumulation

3. This mobile protein can translocate out of the nucleus and bind BECN1

5. This tumor suppressor cannot make up its mind whether to activate or suppress

7. A mammalian reticulophagy receptor

9. An AMPK activator that inhibits autophagy (independent of AMPK)

13. An omegasome protein (some might say “The” omegasome protein)

15. A target of reticulophagy

17. An MTOR activator

19. This receptor is a negative factor with a lot of growth potential

20. A deubiquitinase associated with Machado-Joseph disease

22. The official Drosophila name connotes a place you might go to have a picnic; this is the HGNC name

23. A member of the family binds ATG5, kicking out ATG16L1

24. A Drosophila protein that regulates mitophagy

25. Part of a complex that inhibits MTOR

27. What happens to lysosomes that get into trouble (abbreviation)?

29. The official abbreviation for mitophagosome

31. A lysosomal channel

33. A Shigella protein that helps escape autophagy

34. Generally considered as a positive factor, but recently shown to stimulate MTOR

36. The official abbreviation for autolysosome

37. A yeast RGG motif protein that binds ATG1

39. Homolog of yeast Pep4

40. A sound used to call for pigs and the yeast homolog of EIF2S1

41. Binds Dcp2 in yeast

42. A lectin

44. Mutations in this enzyme are associated with Gaucher disease

46. Part of a pentameric complex that regulates TORC1; there is a rational answer

50. An MTORC1 activator that you can clean up with

52. These small GTPases are involved in many cellular processes

53. Sort of like a protein tattoo; everyone’s getting them

55. A yeast assay for Atg9 trafficking that relies on a deletion of ATG1

57. The official abbreviation for autophagosome

58. A yeast lipase

61. A C. elegans version of a ubiquitin-like protein

62. A GATA1 cofactor that is a positive regulator of transcription

64. A less FAMily friendly name for this reticulophagy receptor

66. A BCL2-family protein that affects BECN1 degradation

67. This process removes protein aggregates

68. A component of the UPR

70. An amino acid that is stored in vacuoles

71. 8, 9, 10 … and it’s down for the count

74. Part of a complex in yeast and mammals that negatively regulates transcription to block mitophagy

75. A receptor that might remind some Californians of a ghost town

78. Part of a yeast complex that stabilizes mRNA during nitrogen starvation

81. A lot of Atg proteins hang out there

85. An often-overlooked intermediate structure

87. Nice places to hang out if you can’t escape into the cytosol

88. An anti-apoptotic protein that inhibits autophagy

89. A cofactor for yeast Ubp3

90. A lysosomotropic compound

91. This protein interacts with BECN1

92. A receptor that functions in hypoxic conditions

94. Sure you can sit in it, but that’s not all

95. An autophagy receptor, no longer considered so neighborly

97. The first example of a biosynthetic role for autophagy

98. A type of selective organelle degradation

99. A protein that is involved in the crosstalk between apoptosis and autophagy

101. Alias for one of the receptors; the name is a hint that it is no longer allowed

106. This domain is found in BCL2-family proteins

107. A soluble SNARE involved in autophagosome fusion

108. Plays a role in yeast pexophagy

110. An inhibitor that competes with ATP

111. A transcription factor regulating LAMP2A and hence CMA

113. An inner mitochondrial membrane receptor

114. A spatial coupling compartment; also, one more thing to do

116. These proteins play a role in peroxisome degradation

118. Involved in S-nitrosylation

120. Usually associated with apoptosis but also suppresses autophagy

123. Just a small part in a big piece of machinery

124. A mutation in this endosomal/lysosomal protein causes inefficient autolysosome clearance

125. An oxygen-regulated transcription factor

126. The second identified cargo of the Cvt pathway

127. Abbreviation for a versatile proteinase

128. There are other members of the family that includes this inhibitor, so the “A” is important

Down

1. A microscopy technique that involves antibodies

2. Autophagy plays a role in the generation of this type of trap

3. A tethering complex

4. This yeast transcriptional activator controls ATG41 among others

6. More commonly used than phosphatidylserine

8. An exoribonuclease downregulated by some viruses

9. This struct is found in plants as well as yeast

10. The beginning of it all for this pathway (see 97 Across)

11. An old-fashioned term for the general type of reagent used in 86 Down

12. A generic name for many of the answers to this crossword

13. A selective type of autophagy, but not for the degradation of yeast

14. This type is not located in the mitochondria

16. A general term for a predatory bird; allows MTORC1 to inhibit ULK1

18. Not all degradation occurs in the lysosome/vacuole

19. A BECN1-binding RTK that inhibits autophagy

21. Sounds like something from Greek mythology but is actually more complex

26. Where a lot of the action happens

27. A collection of autophagy-related processes in cells of the reticulo-endothelial system

28. Expansion in this case can be a problem

30. A serine/threonine protein kinase complex

32. An endogenous neuropeptide that mediates autophagy

33. All the rage, but hard to see

35. A modified form of this protein is the basis for a popular yeast autophagy assay

38. The official abbreviation for 53 Down

39. Mi _ es su _

43. Less cited conjugator

45. An irreversible deconjugator

47. Mess around with PtdIns4P-dependent trafficking and you get this

48. A membrane protein involved in autophagy

49. A pattern recognition receptor

51. Responds to calcium to induce autophagy

53. The workhorse of macroautophagy

54. Inhibits both the class I and class III enzymes

56. This enzyme acetylates ULK1

58. An acronym not as commonly used as that for the mammalian motif but still worth keeping in your sights

59. A RAS-family member

60. It’s not just for diabetes

61. A common interactor (see 58 Down)

63. A phospholipid phosphatase that can generate PtdIns3P

65. A common abbreviation for 128 Across

69. Their potential applications are larger than their size

72. A TBK1 target that acts as a receptor

73. An alias for ATG14

76. A yeast protein similar to SQSTM1

77. A ligand of a pathway that suppresses IFNG-induced autophagy as well as a video game

79. A key part of CLEAR

80. A receptor with a CUE domain

81. Can inhibit 39 Across

82. A similar name to 96 Down but this one has the opposite effect

83. It’s either this or ATG14

84. A better understanding of these could shine a light on lysosome function

86. The abbreviation for a technique that can be used to examine protein-protein interactions

92. A family of transcription factors

93. Commonly used depolarizer, not just in the former USSR

94. A vac by any other name is still a vac; also, the official abbreviation for this compartment

96. An inhibitory component of the PtdIns3K complex

100. These proteins bind PtdIns3P

101. Yes, it is part of the PtdIns3K complex, although often ignored

102. Makes you think of dating in the early 1900s?

103. A cysteine protease inhibitor that has a neuroprotective effect

104. You might say the starter for molecular mammalian autophagy

105. A PX-BAR domain-containing protein

107. Along with its partner, this protein is involved in forming ER contacts with other membranes

109. For some, a raison d’être

110. An autophagy-activating cytokine

112. An alias for DIRAS3, a protein that binds BECN1

115. A yeast protein that interacts with Pho85

117. A kinase upstream of Snf1

119. Abbreviation for a nonspecific inhibitor of autophagy

121. The official abbreviation for 85 Across

122. A modified type of BSA that can be used to follow endocytosis and lysosomal degradation

123. A commonly used autophagy inhibitor

125. A very early enzyme in glycolysis

Disclosure statement

The author declares that he does not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.

Additional information

Funding

The work was supported by NIH grant [GM131919].

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