Lipids implicated in the journey of a secretory granule: from biogenesis to fusion

Abstract

The regulated secretory pathway begins with the formation of secretory granules by budding from the Golgi apparatus and ends by their fusion with the plasma membrane leading to the release of their content into the extracellular space, generally following a rise in cytosolic calcium. Generation of these membrane-bound transport carriers can be classified into three steps: (i) cargo sorting that segregates the cargo from resident proteins of the Golgi apparatus, (ii) membrane budding that encloses the cargo and depends on the creation of appropriate membrane curvature, and (iii) membrane fission events allowing the nascent carrier to separate from the donor membrane. These secretory vesicles then mature as they are actively transported along microtubules toward the cortical actin network at the cell periphery. The final stage known as regulated exocytosis involves the docking and the priming of the mature granules, necessary for merging of vesicular and plasma membranes, and the subsequent partial or total release of the secretory vesicle content. Here, we review the latest evidence detailing the functional roles played by lipids during secretory granule biogenesis, recruitment, and exocytosis steps. In this review, we highlight evidence supporting the notion that lipids play important functions in secretory vesicle biogenesis, maturation, recruitment, and membrane fusion steps. These effects include regulating various protein distribution and activity, but also directly modulating membrane topology. The challenges ahead to understand the pleiotropic functions of lipids in a secretory granule's journey are also discussed. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015).

A Phosphatidic Acid (PA) conveyor system of continuous intracellular transport from cell membrane to nucleus maintains EGF receptor homeostasis

“…Newly synthesized EGFR is then shuttled through the Golgi to the plasma membrane through vesicles. As known, lipids play a fundamental role in intracellular trafficking and active transport, particularly in the Golgi and exocytosis [42]. However, it comes to a point in which there is abundant accumulation of PA in the nucleus and/or a loss in EGF signal.…”

An endosomal syntaxin and the AP-3 complex are required for formation and maturation of candidate lysosome-related secretory organelles (mucocysts) inTetrahymena thermophila

“…These proteins associate with membrane proteins and lipids, which, in some as poorly understood way, directs the ensemble to budding immature DCGs (Orci et al. , 1987; Chanat and Huttner, 1991; Arvan and Castle, 1998; Tanguy et al. , 2016).…”

Membrane shaping by actin and myosin during regulated exocytosis

“…It comprises of a dense layer of actomyosin fibres adjacent to the plasma membrane which is crucial in regulating the access of secretory vesicles to their docking and fusion sites in neurosecretory cells (Trifaro et al, 2008(Trifaro et al, , 1992. Considerable efforts have been undertaken to decipher the function of the cortical actin network and supporting proteins such as myosins (Berg et al, 2001;, adhesion molecules and small GTPases (Gasman et al, 2003;Hall and Nobes, 2000) as well as lipid modulators (Tanguy et al, 2016) in regulated exocytosis. The close proximity of the cortical actin network to the plasma membrane implicates an intricate interplay between actomyosin and both exo-and endocytic membrane structures.…”