Concept 38 Development balances cell growth and death.

HI! Programmed cell death in C. elegans is controlled through the interaction between ced-3, the gene that promotes cell death, and ced-9, the gene that promotes cell survival. A third gene, ced-4, is also known to play a role. This is one model of how these proteins work together. CED-9 is a receptor that binds CED-4. If the cell is supposed to die, then another protein interferes with the CED-9/CED-4 interaction. This releases CED-4, which then dimerizes and binds another CED-4 protein. This CED-4 complex can now bind CED-3 proteins. Bringing the CED-3 proteins together activates them. CED-3 binds to and degrades CED-9. Other proteins activated by CED-3 will now attack and kill the cell. What happens in mutants without functioning CED-3 and CED9? The double mutant should have the same number of cells as the wildtype. (No, there is no functioning CED-3, so no cell death.) The double mutant has no CED-3, so there is no cell death. (That is correct.) Without CED-3 or CED-9, random cell deaths occur. (No, there is no functioning CED-3, so no cell death.) The double mutant should have more cell deaths than wild-type. (No, there is no functioning CED-3, so no cell death.) There is no cell death in mutants without the functioning CED-3 protein. These mutations are known as loss-of-function mutations. Whether CED-9 is present or not does not affect the phenotype of the double mutant. What do you think would happen in a mutant with no functioning CED-3, CED-4 and CED-9? The triple mutant should have the same number of cells as the wildtype. (No, there is no functioning CED-3, so no cell death.) The triple mutant has no CED-3, so there is no cell death. (That is correct) Without CED-3, CED-4 or CED-9, random cell deaths occur. (No, there is no functioning CED-3, so no cell death.) The triple mutant should have more cell deaths than wildtype. (No, there is no functioning CED-3, so no cell death.) In the triple mutant CED-3 is non-functional, so there is no cell death. Whether CED-9 or CED-4 is present or not does not affect the phenotype of the triple mutant. In one kind of ced-9 mutant, known as "gain of function," there are no cell deaths. How might this be explained? CED-3 is non-functional. (No, only CED-9 is affected in this mutant.) CED-9 binds tightly to, and does not release, CED-4. (That is correct) CED-9 is not exported as a receptor. (No, if CED-9 is not exported as a receptor, there would be free CED-4 to activate CED-3.) None of the above. (No, there is a correct answer.) If ced-9 is mutated such that no cell death occurs, one possibility is that the binding site of the CED-9 protein has changed. CED-9 now binds CED-4 so tightly that CED-4 never gets released. CED-3 would then never get activated to cause cell death. If a double mutant is made carrying the gain of function CED-9 mutation and another gain of function CED-3 mutation, cell death will occur. What do you think might be happening? CED-9 cannot bind CED-4. (No, if true, CED-3 does not need to be mutated for cell death to occur.) CED-3 cannot bind to the CED-4 dimer. (No, if true, then CED-3 cannot be activated.) CED-3 is activated without binding to the CED-4 dimer. (That is correct) CED-3 is degrading CED-4. (No, CED-3 needs CED-4 for activation.) CED-3 must be activated for cell death to occur. In a mutant where CED-4 is not available, CED-3 must be activated some other way. Mammalian cells have cell death genes. In humans, ced-3 and ced-9 are most similar to caspase-9 and bcl-2, respectively. ced-4 is most similar to apaf-1. Which of these cases stop cell death and possibly lead to cancerous growths? A non-functioning CASPASE-9. (Yes, this could stop cell death.) BCL-2 is highly expressed. (Yes, this could stop cell death.) APAF-1 cannot dimerize. (Yes, this could stop cell death.) All of the above. (That is correct) Programmed cell death is dependent on the interaction of all these genes. Although the mechanism is similar, in mammalian systems there are evenmore cell death genes and thus more levels of regulation. CONGRATULATIONS!!! YOU'RE SO SMART!