Q.39 Which one or more of the following statements is/are correct regarding the transport
and retention of proteins in different cell organelles?
(A) Mannose 6–phosphate residues are involved in targeting proteins to lysosomes.
(B) Transport of proteins into the mitochondrial compartment is aided by positively
charged amino acid residues at the N–terminus and internal hydrophobic segments.
(C) The retention of protein in the ER lumen requires the KDEL sequence motif at the
C–terminus.
(D) Nuclear proteins are transported in an unfolded conformation and the nuclear
localization signal sequence is subsequently cleaved by peptidases in the
nucleoplasm.

Mannose 6-phosphate residues target lysosomal enzymes via receptors in the trans-Golgi network, confirming option (A) as correct. Options (B), (C), and (D) align with standard mechanisms of mitochondrial import, ER retention, and nuclear transport, respectively, making all statements accurate for CSIR NET Life Sciences preparation.

Option Analysis

(A) Lysosomal Targeting

Mannose 6-phosphate (M6P) residues on high-mannose N-glycans of lysosomal hydrolases are added in the cis-Golgi by phosphotransferase and uncovered by glucosidase II. These residues bind M6P receptors (MPR46 and MPR300) in the trans-Golgi network, directing clathrin-coated vesicles to late endosomes that mature into lysosomes.​

(B) Mitochondrial Import

Mitochondrial preproteins feature an N-terminal amphipathic α-helix targeting signal rich in positively charged residues (Arg, Lys) and flanked by hydrophobic segments, enabling recognition by cytosolic chaperones, TOM complex translocation across the outer membrane, and TIM23 complex insertion into the inner membrane.​

(C) ER Retention

Soluble ER luminal proteins bear the C-terminal KDEL tetrapeptide (Lys-Asp-Glu-Leu), which binds KDEL receptors (KDELR1-3) in the Golgi under slightly acidic conditions. Receptor-cargo complexes recycle via COPI vesicles back to the ER, preventing secretory pathway escape.​

(D) Nuclear Transport

Nuclear proteins enter via nuclear pore complexes in a folded or partially folded state, guided by nuclear localization signals (NLS) recognized by importins (e.g., importin α/β). NLS remains uncleaved post-import, allowing repeated shuttling after cell division, unlike cleavable signals in mitochondria or ER.​

Correct Answer

All options (A), (B), (C), and (D) are correct.

Protein transport and retention in cell organelles ensures precise localization of enzymes and structural proteins, critical for cellular function in topics like vesicular trafficking for CSIR NET Life Sciences. This guide breaks down key signals: mannose 6-phosphate for lysosomes, N-terminal motifs for mitochondria, KDEL for ER, and NLS for nucleus.

Lysosome Targeting via Mannose 6-Phosphate

Lysosomal hydrolases gain mannose 6-phosphate (M6P) in the Golgi, binding M6P receptors for endosomal delivery. Defects cause lysosomal storage disorders, highlighting its exam relevance.​

Mitochondrial Protein Import Signals

Positively charged N-terminal presequences with hydrophobic domains drive unfolding and translocation through TOM/TIM complexes.​

• Amphipathic helix formation aids membrane potential-dependent import.

• Matrix processing peptidase cleaves the signal post-translocation.

ER Retention with KDEL Sequence

The C-terminal KDEL motif retrieves escaped ER proteins from Golgi via COPI vesicles and KDELR binding.​

Nuclear Localization and NLS Fate

NLS directs importin-mediated entry through nuclear pores; proteins arrive folded, and NLS persists for recycling.​