Cellular transport of proteins is very important in order for a cell to function

Question

Cellular transport of proteins is very important in order for a cell to function properly. For each of the mutations below,

(1) explain what type of transport will be affected by explaining the correct transport process and where the problem will arise and

(2) where the proteins that are transported incorrectly will be found.

A mutation in N-acetyl transferase, the enzyme that adds N-linked glycosylation to proteins.

A mutation in the TOM complex

A mutation that causes GTP to not be hydrolyzed in the cytosol

Explanation / Answer

1). More than 130 different mutations in the gap junction integral plasma membrane protein connexin32 (Cx32) have been linked to the human peripheral neuropathy X-linked Charcot–Marie–Tooth disease (CMTX).

How these various mutants are processed by the cell and the mechanism(s) by which they cause CMTX are unknown. To address these issues, we have studied the intracellular transport, assembly, and degradation of three CMTX-linked Cx32 mutants stably expressed in PC12 cells.

Each mutant had a distinct fate: E208K Cx32 appeared to be retained in the endoplasmic reticulum (ER), whereas both the E186K and R142W mutants were transported to perinuclear compartments from which they trafficked either to lysosomes (R142W Cx32) or back to the ER (E186K Cx32).

Despite these differences, each mutant was soluble in nonionic detergent but unable to assemble into homomeric connexons. Degradation of both mutant and wild-type connexins was rapid (t1/2 < 3 h) and took place at least in part in the ER by a process sensitive to proteasome inhibitors.

The mutants studied are therefore unlikely to cause disease by accumulating in degradation-resistant aggregates but instead are efficiently cleared from the cell by quality control processes that prevent abnormal connexin molecules from traversing the secretory pathway.

2). A mutation in N-acetyl transferase, the enzyme that adds N-linked glycosylation to proteins.

i.e.,Where during the mutation occurs in the cellular transport of the protein, it affects the enzyme that adds N- linked glycosylation to proteins.

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