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.