PROTEIN SECRETION FROM MOUSE SKELETAL-MUSCLE - COUPLING OF INCREASED EXOCYTOTIC AND ENDOCYTOTIC ACTIVITIES IN DENERVATED MUSCLE

The secretion of proteins labelled by incorporation of radioactive ami no acids was studied in innervated and 10 to 13-day-denervated mouse s keletal muscle. The secretion of H-3-leucine-labelled proteins, expres sed per mg muscle wet weight, increased after denervation, and the kin etics of the secretory process was also altered in denervated muscle. Separation of secreted S-35-methionine-labelled proteins by sodium dod ecyl sulphate polyacrylamide gel electrophoresis followed by autoradio graphy revealed some denervation-induced alterations in the pattern of secreted proteins. The secretion from both innervated and denervated muscle was highly temperature sensitive and was reversibly inhibited b y brefeldin A, a drug that blocks forward membrane transport from the endoplasmic reticulum/Golgi apparatus. This drug was also found to inh ibit the uptake of fluorescein isothiocyanate-labelled dextran in dene rvated muscle but had no effect on the endocytotic activity of innerva ted muscle. This lends support to the hypothesis that the increased en docytotic activity in denervated muscle is coupled to a high secretory activity.