Practice question

Protein sorting depends on presence of N-terminal signal sequence or internal transmembrane domain. Secretory proteins like insulin, lysosomal cathepsins, plasma membrane receptors and Golgi glycosyltransferases harbor hydrophobic signals recognized by signal recognition particle leading to Sec61 engagement and translocation into ER lumen or membrane, then onward transport, removed from cytosol. Absence of signal leaves nascent chain completing synthesis on free ribosomes in cytoplasm where folding by Hsp70 and TRiC chaperonin occurs. Cytoskeletal proteins actin forty three kDa forming seven nanometer microfilaments and spectrin alpha beta tetramer crosslinking cortical actin belong to this cytosolic class, assembling into meshwork under plasma membrane regulating shape, not entering ER. Experimental fractionation shows actin mRNA enriched in free polysomes versus membrane-bound polysomes, puromycin release independent of microsomes, resistance to protease protection assay. Thus actin and spectrin exemplify ribosome-free cytoplasmic proteins distinct from secretory cohort that require ER entry for modifications. Integration with cell cycle kinases, calcium signaling and mechanical cues ensures coordinated remodeling during growth, migration and differentiation.