HIGHLIGHTS
SUMMARY
Secretory proteins control human metabolism and physiology, and their mistargeting causes several diseases, including type 2 diabetes (T2D), neurodegenerative disorders, and cancer (Uhlén et_al, 2019; Frantz et_al, 2010). Early electron microscopy imaging showed that secretory granules (SGs) contain an electron-dense core that is modified/ concentrated in sequential steps starting in the Golgi apparatus (Orci et_al, 1987; Palade, 1975; Farquhar et_al, 1978; Farquhar and Wellings, 1957), wherein granule-destined proteins are sorted and packaged into short-lived vesicular intermediates known as immature SGs (ISGs; Tooze et_al, 1991). Remarkably, proinsulin and its processing enzymes . . .
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