Abstract
The biogenesis, maturation, and exocytosis of secretory granules in interphase cells have been well documented, whereas the distribution and exocytosis of these hormone-storing organelles during cell division have received little attention. By combining ultrastructural analyses and time-lapse microscopy, we here show that, in dividing PC12 cells, the prominent peripheral localization of secretory granules is retained during prophase but clearly reduced during prometaphase, ending up with only few peripherally localized secretory granules in metaphase cells. During anaphase and telophase, secretory granules exhibited a pronounced movement towards the cell midzone and, evidently, their tracks colocalized with spindle microtubules. During cytokinesis, secretory granules were excluded from the midbody and accumulated at the bases of the intercellular bridge. Furthermore, by measuring exocytosis at the single granule level, we showed, that during all stages of cell division, secretory granules were competent for regulated exocytosis. In conclusion, our data shed new light on the complex molecular machinery of secretory granule redistribution during cell division, which facilitates their release from the F-actin-rich cortex and active transport along spindle microtubules.
Highlights
Secretory granules (SGs) are the hormone and neuropeptide containing organelles of neuroendocrine cells that release their content upon depolarization-induced, Ca2+-dependent exocytosis
By measuring exocytosis at the single granule level, we showed, that during all stages of cell division, secretory granules were competent for regulated exocytosis
It was shown that SGs, which are not consumed by exocytosis, are eventually removed from the cell cortex and replaced by newer ones [5]
Summary
Secretory granules (SGs) are the hormone and neuropeptide containing organelles of neuroendocrine cells that release their content upon depolarization-induced, Ca2+-dependent exocytosis. The biogenesis and stimulated secretion of these high-copy number organelles have been intensively studied in various interphase cell models [1,2,3,4,5]. In the case of neuroendocrine PC12 cells, real-time studies revealed that shortly after their biogenesis at the trans-Golgi network, SGs undergo a unidirectional, microtubule-dependent transport to the plasma membrane (PM) [3]. SGs of PC12 and MIN6 cells were found to undergo a myosin Vadependent movement and restriction in the F-actin-rich cortex, where they complete their maturation [7]. It was shown that SGs, which are not consumed by exocytosis, are eventually removed from the cell cortex and replaced by newer ones [5]
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