Differential routing of coexisting neuropeptides in vasopressin neurons

Landry, Marc; Vila-Porcile, Évelyne; Hökfelt, T; Calas, A.

doi:10.1046/j.1460-9568.2003.00001.x

Cited by 35 publications

(49 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Voltage-gated potassium channels are known to form tetramers while still attached to ribosomes (Lu et al, 2001). Magnocellular neurons have regions of ER devoted to the synthesis of vasopressin versus galanin, which could result in elevated local concentrations (Landry et al, 2003).…”

Section: Self-aggregation: a Default Mechanism For Cargo Protein Sortingmentioning

confidence: 99%

Not All Secretory Granules Are Created Equal: Partitioning of Soluble Content Proteins

Sobota

Ferraro

Back

et al. 2006

MBoC

View full text Add to dashboard Cite

Secretory granules carrying fluorescent cargo proteins are widely used to study granule biogenesis, maturation, and regulated exocytosis. We fused the soluble secretory protein peptidylglycine ␣-hydroxylating monooxygenase (PHM) to green fluorescent protein (GFP) to study granule formation. When expressed in AtT-20 or GH3 cells, the PHM-GFP fusion protein partitioned from endogenous hormone (adrenocorticotropic hormone, growth hormone) into separate secretory granule pools. Both exogenous and endogenous granule proteins were stored and released in response to secretagogue. Importantly, we found that segregation of content proteins is not an artifact of overexpression nor peculiar to GFP-tagged proteins. Neither luminal acidification nor cholesterol-rich membrane microdomains play essential roles in soluble content protein segregation. Our data suggest that intrinsic biophysical properties of cargo proteins govern their differential sorting, with segregation occurring during the process of granule maturation. Proteins that can self-aggregate are likely to partition into separate granules, which can accommodate only a few thousand copies of any content protein; proteins that lack tertiary structure are more likely to distribute homogeneously into secretory granules. Therefore, a simple "self-aggregation default" theory may explain the little acknowledged, but commonly observed, tendency for both naturally occurring and exogenous content proteins to segregate from each other into distinct secretory granules. INTRODUCTIONThe cellular life of secretory proteins begins with the cotranslational translocation of their nascent polypeptide chains into the lumen of the endoplasmic reticulum (ER). These proteins then proceed in the anterograde direction, through the Golgi complex and into the trans-Golgi network (TGN), which is considered a "sorting station" for secretory proteins (Farquhar and Palade, 1981). At the TGN, vesicles destined for different subcellular compartments bud while acquiring their cargo. In all cell types, a "constitutive secretory pathway" delivers soluble and membrane secretory proteins necessary for housekeeping functions to the appropriate compartment (e.g., plasma membrane or endosomes/ lysosomes; Turner and Arvan, 2000). Besides this constitutive pathway, specialized cell types such as endocrine, exocrine, neuroendocrine cells, and neurons possess a "regulated pathway" in which specialized organelles, the secretory granules, store proteins for release in response to an incoming signal (Arvan and Castle, 1998). The soluble proteins found in constitutive vesicles and regulated secretory granules differ, and the processes responsible for this segregation are the object of intensive investigation.Two models, "sorting for entry" and "sorting by retention," both having experimental support, have been proposed to explain how sorting of soluble content proteins occurs (Arvan and Castle, 1998). The sorting for entry hypothesis postulates the existence of one or more "membrane receptors" able to selectivel...

show abstract

Section: Self-aggregation: a Default Mechanism For Cargo Protein Sortingmentioning

confidence: 99%

Not All Secretory Granules Are Created Equal: Partitioning of Soluble Content Proteins

Sobota

Ferraro

Back

et al. 2006

MBoC

View full text Add to dashboard Cite

show abstract

“…In various cell types, however, storage of secretory proteins has been shown to occur, completely or in large part, within distinct SGs. Examples are: (1) three peptides from the egg-laying hormone precursor processing of Aplysia californica, stored in three types of SGs [3,4]; (2) growth hormone, prolactin and the granin secretogranin II of the acidophilic cow pituitary cells, each contained in a distinct type of SG [5]; and (3) galanin and vasopressin of neurohypophysial neurons, stored in two distinct and one mixed SG population [6]. It remains largely unknown whether the exocytosis of distinct SGs in single cells occurs under the same or different controls.…”

Section: Introductionmentioning

confidence: 99%

Beta cell chromogranin B is partially segregated in distinct granules and can be released separately from insulin in response to stimulation

et al. 2008

View full text Add to dashboard Cite

Aims/hypothesis We investigated, in three beta cell lines (INS-1E, RIN-5AH, betaTC3) and in human and rodent primary beta cells, the storage and release of chromogranin B, a secretory protein expressed in beta cells and postulated to play an autocrine role. We asked whether chromogranin B is stored together with and discharged in constant ratio to insulin upon various stimuli. Methods The intracellular distribution of insulin and chromogranin B was revealed by immunofluorescence followed by three-dimensional image reconstruction and by immunoelectron microscopy; their stimulated discharge was measured by ELISA and immunoblot analysis of homogenates and incubation media. Results Insulin and chromogranin B, co-localised in the Golgi complex/trans-Golgi network, appeared largely segregated from each other in the secretory granule compartment. In INS-1E cells, the percentage of granules positive only for insulin or chromogranin B and of those positive for both was 66, 7 and 27%, respectively. In resting cells, both insulin and chromogranin B were concentrated in the granule cores; upon stimulation, chromogranin B (but not insulin) was largely redistributed to the core periphery and the surrounding halo. Strong stimulation with a secretagogue mixture induced parallel release of insulin and chromogranin B, whereas with 3-isobutyl-1-methylxantine and forskolin ± high glucose release of chromogranin B predominated. Weak, Ca 2+ -dependent stimulation with ionomycin or carbachol induced exclusive release of chromogranin B, suggesting a higher Ca 2+ sensitivity of the specific granules. Conclusions/interpretation The unexpected complexity of the beta cell granule population in terms

show abstract

“…However, it is possible that GAL could be released by a different pattern of afferent stimulation to inhibit eEPSCs. This is feasible as GAL and AVP are packaged in different vesicles in MCN dendrites (Landry et al 2003). For example, continuous afferent stimulation at 1 Hz causes the release of adenosine, which depresses eEPSCs (Oliet and Poulain 1999), but this effect is entirely reversed by adenosine antagonists.…”

Section: Source Of Galaninmentioning

confidence: 99%

“…GAL levels are known to decline in the SON in the dehydrated animal (Meister et al 1990). Since GAL containing vesicles are preferentially directed to the dendrites (Landry et al 2003) it is likely (but not yet proven) that GAL is released into the extracellular space of the SON. Additional sources of GAL are the afferent fibers that display GAL immunoreactivity (Levin et al 1987;Melander et al 1986; Okere and Waterhouse 2003).…”

Section: Source Of Galaninmentioning

confidence: 99%

“…Along with that for the neurohypophysial peptides, mRNA for GAL has been localized to MCNs and the peptide has been localized in the somata and dendrites of MCNs (Bonnefond et al 1990;Landry et al 2003;Okere and Waterhouse 2003;Sanchez et al 2001) in vesicles largely distinct, but sometime co-localized with those containing AVP. In fact, there is evidence that GAL containing vesicles are preferentially directed toward the dendrites (Landry et al 2003). This localization of GAL in dendrites makes it a possible candidate as a dendritically released transmitter similar to what has been described for AVP and OXT.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Galanin Modulates Neuronal and Synaptic Properties in the Rat Supraoptic Nucleus in a Use and State Dependent Manner

Kozoriz

Kuzmiski²,

Hirasawa³

et al. 2006

Journal of Neurophysiology

View full text Add to dashboard Cite

. Galanin modulates neuronal and synaptic properties in the rat supraoptic nucleus in a use and state dependent manner. J Neurophysiol 96: 154 -164, 2006; doi:10.1152/jn.01028.2005. The magnocellular neurons of the hypothalamic supraoptic nucleus (SON) synthesize and secrete oxytocin (OXT) and vasopressin (AVP) from their dendrites. These peptides, and several other neurotransmitters, have been shown to modulate afferent glutamatergic neurotransmission in the SON. The neuropeptide, galanin (GAL) is also localized in SON magnocellular neurons and in afferent fibers in the nucleus. We show that GAL dose-dependently reduces evoked excitatory postsynaptic currents (eEPSCs), alters paired pulse ratio and decreases mEPSC frequency, but not amplitude or decay kinetics in both OXT and AVP neurons. GAL therefore modulates excitatory neurotransmission at a likely presynaptic receptor. Neither OXT/AVP, GABA B nor cannabinoid antagonists blocked this effect. A GAL2/3 agonist mimicked GAL's action while GAL1 antagonist did not block GAL's effect, suggesting that GAL2/3 receptors mediate the presynaptic effect. In nondehydrated rats GAL causes a small postsynaptic response, as assessed by input resistance measurements. When the rats were water deprived for 2 days the presynaptic response to GAL was unaltered; however, the postsynaptic decrease in input resistance and hyperpolarization was increased, an effect consistent with a previously described increase in GAL1 receptor expression in dehydration. A GAL1 receptor antagonist blocked the postsynaptic effects. Last, when a train of eEPSCs was elicited, GAL was found to inhibit the earlier events in a train but not the latter. This indicates that GAL may modulate a single synaptic event more effectively than trains of synaptic inputs, thereby acting as a high-pass filter.

show abstract

Differential routing of coexisting neuropeptides in vasopressin neurons

Cited by 35 publications

References 0 publications

Not All Secretory Granules Are Created Equal: Partitioning of Soluble Content Proteins

Not All Secretory Granules Are Created Equal: Partitioning of Soluble Content Proteins

Beta cell chromogranin B is partially segregated in distinct granules and can be released separately from insulin in response to stimulation

Galanin Modulates Neuronal and Synaptic Properties in the Rat Supraoptic Nucleus in a Use and State Dependent Manner

Contact Info

Product

Resources

About