Question

6. (4pts) Indicate if you “AGREE” or DISAGREE” with the following statements. Explain your reasoning.

A) (1pt) ATP hydrolysis is necessary for actin treadmilling. (4 sentence max)

B) (1pt) Late endosomes are converted to mature lysosomes by an increase in their internal pH. (4 sentence max)

C) (1pt) Lysosomal membranes contain a proton pump that utilizes the energy of ATP hydrolysis to pump protons out of the lysosome, thereby maintaining the lumen at a low pH. (4 sentence max)

D) (1pt) If cells were treated with a weak base which neutralizes the pH of organelles, it is expected that M6P receptors would accumulate in the Golgi due to the M6P receptors inability to bind lysosomal enzymes. (4 sentence max)

Answer 1

A) DISAGREE

Actin filament polymerization involves 3 steps. First is the lag phase in which ATP--G-actin monomers aggregate into an oligomer of 3-4 subunits to form a stable seed or nucleus. The second phase is elongation which is achieved by the addition of monomers at both ends. In the third phase, ends of the actin filament are steady-state with the monomeric ATP--G-protein. After their incorporation in the filament, subunits slowly hydrolyze ATP to form stable ADP--F-actin. But, ATP hydrolysis is not essential polymerization as G-actin containing ADP or nonhydrolyzable ATP analog can also polymerize into filaments.

B) DISAGREE

Late endosomes undergo maturation upon fusion with lysosomes and during this process undergo a series of changes. There is an exchange of membrane components, they move to the perinuclear area, the formation of intraluminal vesicles, drop-in luminal pH (acidification) from pH 6.0 to pH 6.0-4.6, acquisition of lysosomal components and change in size and morphology.

C) DISAGREE

Lysosomes contain acid hydrolases to digest macromolecules and for the optimal activity, they require acidic environment so lysosomes maintain a pH of 5.0 for the same. An H+ pump in the lysosomal membrane utilizes energy released by ATP hydrolysis to pump H+ into the lysosome (not out of the lysosome as mentioned in the question) thereby maintaining the acidic pH of the lumen.

D) AGREE

Lysosomal hydrolases and membrane proteins are synthesized in the ER and transported via the Golgi apparatus to the trans-Golgi network. Lysosomal hydrolases carry M6P (mannose-6-phosphate) markers that are recognized by M6P receptors in the trans-Golgi network. M6P receptor proteins bind to hydrolases on the luminal side of the membrane. This happens at pH 6.5-6.7. Subsequently, M6P receptor proteins dissociate from hydrolases and deliver the hydrolases to the late endosomes. This happens at pH of 6.0. So, as per the question, if pH is neutralized, M6P receptors will not be able to bind to hydrolases as they require a pH of 6.5 to 6.7 for the same and will lead to the accumulation of M6P receptors in Golgi.

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