REGULATION OF COMPENSATORY ENDOCYTOSIS

When initially performing the cell-attached capacitance measurements I observed a great number of endocytotic events, and in many cases I could observe the endocytotic fission pore.  This therefore allows me to investigate the regulation of endocytotic fission in these cells.  Also, membrane recycling of SLMVs and LDCVs by ‘kiss-and-run’ exocytosis is being investigated.

In every cell that secretes products via exocytosis, whether it be neurosecretory, endocrine or exocrine, the vesicle membrane that is added to the plasma membrane must be taken back up into the cell.  Therefore, in cells that undergo stimulated exocytosis (for example pancreatic b-cell vesicles undergo exocytosis in response to glucose– for a review go here) the re-internalization of membrane by endocytosis must also be up-regulated.  There is controversy as to how the excess membrane is taken back up into the cell.

In the classical view exocytosis proceeds completely, that is when a vesicle fuses with the membrane it completely flattens out such that it’s membrane components disperse into the plasma membrane.  Endocytosis then occurs at some distant site in a clathrin and dynamin-dependent manner.  Endocytotic vesicles retrieved in this manner may recycle directly by the re-uptake of neurotransmitter or via an endosomal compartment where the vesicle components are re-sorted and new vesicle are formed for transport back to the cell surface.  If this view is correct, then all insulin containing LDCVs must be produced at some point within the cell interior for latter transport to the plasma membrane.  This type of endocytosis is thought to have Ca²⁺-dependent and independent steps.

A more controversial view of membrane recycling comes in the form of ‘kiss-and-run’ exocytosis.  In this view, an exocytotic vesicle does not flatten completely into the plasma membrane, but instead a small fusion pore forms for a brief period that allows the vesicular constituents to either fully or partially escape (perhaps even selectively, if the fusion pore acts as a molecular filter).  This scheme would allow insulin containing LDCVs to fuse transiently with the membrane and then pinch-off remaining in place (perhaps with some or all of it’s insulin cargo still inside) for subsequent fusion events.

There is evidence that both of these pathways of membrane recycling may be important.  There are several reviews on this for more information:

References:

Rutter and Tsuboi (2004) Kiss and run exocytosis of dense core secretory vesicles. Neuroreport 15:79-81

Artalejo et al. (1998) Secretion: dense-core vesicles can kiss-and-run too. Curr Biol 8:R62-65

Hannah et al. (1999) Synaptic vesicle biogenesis. Annu Rev Cell Dev Biol 15:177-98

Murthy and De Camilli (2003) Cell biology of the presynaptic terminal. Annu Rev Neurosci 26:701-28

Cousin (2001) Synaptid vesicle endocytosis: Calcium works overtime in the nerve terminal. Mol Neurobiol 21:1-14

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