Regulated secretion

Constitutive secretion Regulated secretion Neuronal secretion... 

Burgess TL, Kelly RB (1987) Constitutive and regulated secretion of proteins. Annu Rev Cell Biol 3 243-293... 

Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP) is a 38-amino acid peptide (PACAP-38), which is widely expressed in the central nervous system. PACAP is most abundant in the hypothalamus. It is also found in the gastrointestinal tract, the adrenal gland and in testis. Its central nervous system functions are ill-defined. In the periphery, PACAP has been shown to stimulate catecholamine secretion from the adrenal medulla and to regulate secretion from the pancreas. Three G-protein coupled receptors have been shown to respond to PACAP, PAQ (PACAP type I) specifically binds PACAP, VPACi and VPAC2 also bind vasoactive intestinal peptide (VDP). Activation of PACAP receptors results in a Gs-mediated activation of adenylyl cyclase. 

As with gastric secretion, nervous stimulation and hormones regulate secretion from the pancreas. During the cephalic phase and gastric phase, the pancreas secretes a low-volume, enzyme-rich fluid mediated by the vagus nerve. 

Rhoads, M.L. and Fetterer, R.H. (1995) Developmentally regulated secretion of cathepsin L-like proteases by Haemonchus contortus. Journal for Parasitology 81, 505-512. 

SYNAPTIC VESICLE TRAFFICKING IS A SPECIALIZED FORM OF REGULATED SECRETION AND RECYCLING OPTIMIZED FOR SPEED AND EFFICIENCY 158... 

Vesicular proteins and lipids that are destined for the plasma membrane leave the TGN sorting station continuously. Incorporation into the plasma membrane is typically targeted to a particular membrane domain (dendrite, axon, presynaptic, postsynaptic membrane, etc.) but may or may not be triggered by extracellular stimuli. Exocytosis is the eukaryotic cellular process defined as the fusion of the vesicular membrane with the plasma membrane, leading to continuity between the intravesicular space and the extracellular space. Exocytosis carries out two main functions it provides membrane proteins and lipids from the vesicle membrane to the plasma membrane and releases the soluble contents of the lumen (proteins, peptides, etc.) to the extracellular milieu. Historically, exocytosis has been subdivided into constitutive and regulated (Fig. 9-6), where release of classical neurotransmitters at the synaptic terminal is a special case of regulated secretion [54]. 

The constitutive pathway has not been studied as intensively as regulated secretion [54]. In particular, relatively little is known about targeting and regulatory mechanisms for these transport vesicles. Clathrin seems not to be directly involved in the constitutive secretory pathway. Antibodies that disrupt clathrin assembly in vitro inhibit endocytosis, but constitutive exocytosis is not affected [63]. 

Secretory cells, including neurons, also possess a specialized regulated secretory pathway. Vesicles in this pathway have soluble proteins, peptides or neurotransmitters stored and concentrated within secretory vesicles. At that point, these vesicles are actively transported to a site for extracellular delivery in response to a specific extracellular signal. Exocytosis through regulated secretion accomplishes different functions, including the... 

At least two classes of regulated secretion can be defined [54]. The standard regulated secretion pathway is common to all secretory cells (i.e. adrenal chromaffin cells, pancreatic beta cells, etc.) and works on a time scale of minutes or even longer in terms of both secretory response to a stimulus and reuptake of membranes after secretion. The second, much faster, neuron-specific form of regulated secretion is release of neurotransmitters at the synapse. Release of neurotransmitters may occur within fractions of a second after a stimulus and reuptake is on the order of seconds. Indeed, synaptic vesicles may be recycled and ready for another round of neurotransmitter release within 1-2 minutes [64]. These two classes of regulated secretion will be discussed separately after a consideration of secretory vesicle biogenesis. 

Since FSH and LH are involved in spermatogenesis, hypothalamic control of their release by the pituitary is important for testicular function. Both FSH and LH are secreted in a pulsatile fashion from the pituitary. Inhibin produced by Sertoli cells has the most important negative feedback effect on FSH secretion, while testosterone exerts negative feedback effects on secretion of GnRH by the hypothalamus, thus regulating secretion of LH and, to a lesser extent, FSH. 

Nicholas, G., Thomas, M., and Langley, B. (2002). Titin-cap associates with, and regulates secretion of, myostatin./ Cell. Physiol. 193, 120-131. 

Taupenot, L. (2007). Analysis of regulated secretion using PC12 cells. Curr. Protoc. Cell Biol. 36, 15.12.1-15.12.13. 

Robert SJ, Zugaza JL, Fischmeister R, Gardier AM, Lezoualc h F. The human serotonin 5-HT4 receptor regulates secretion of non-amyloidogenic precursor protein. J Biol Chem 2001 276 44,881-44,888. 

Maillet M, Robert SJ, Cacquevel M, et al. Crosstalk between Rapl and Rac regulates secretion of sAPPa. Nat Cell Biol 2003 5 633-639. 

Ogg, S.L. Weldon, A.K., Dobbie, L., Smith, A.J.H., Mather, I.H. 2004. Expression of butyr-ophilin (Btnlal) in lactating mammary gland is essential for the regulated secretion of milk-lipid droplets. Proc. Natl. Acad. Sci. USA. 101, 10084-10089. 

---