Molecular Aspects of Secretory Granule Exocytosis by Neurons and Endocrine Cells

Neuronal communication and endocrine signaling are fundamental for integrating the function of tissues and cells in the body. Hormones released by endocrine cells are transported to the target cells through the circulation. By contrast, transmitter release from neurons occurs at specialized intercellular junctions, the synapses. Nevertheless, the mechanisms by which signal molecules are synthesized, stored, and eventually secreted by neurons and endocrine cells are very similar. Neurons and endocrine cells have in common two different types of secretory organelles, indicating the presence of two distinct secretory pathways. The synaptic vesicles of neurons contain excitatory or inhibitory neurotransmitters, whereas the secretory granules (also referred to as dense core vesicles, because of their electron dense content) are filled with neuropeptides and amines. In endocrine cells, peptide hormones and amines predominate in secretory granules. The function and content of vesicles, which share antigens with synaptic vesicles, are unknown for most endocrine cells. However, in B cells of the pancreatic islet, these vesicles contain GABA, which may be involved in intrainsular signaling.' Exocytosis of both synaptic vesicles and secretory granules is controlled by cytoplasmic calcium. However, the precise mechanisms of the subsequent steps, such as docking of vesicles and fusion of their membranes with the plasma membrane, are still incompletely understood. This contribution summarizes recent observations that elucidate components in neurons and endocrine cells involved in exocytosis. Emphasis is put on the intracellular aspects of the release of secretory granules that recently have been analyzed in detail

Xanthogranuloma of the intrasellar region presenting in pituitary dysfunction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Differentiation of cystic mass lesions of the sellar and parasellar regions may pose a diagnostic dilemma for physicians, neurosurgeons, radiologists and pathologists involved in treating patients with these entities. A considerable number of tumors previously identified as craniopharyngiomas may, in fact, have been xanthogranulomas. We report a case of pituitary dysfunction caused by xanthogranuloma of the intrasellar region.</p> <p>Case presentation</p> <p>A 47-year-old man of Japanese descent presented to our institution with a tumor located exclusively in the intrasellar region which manifested as severe hypopituitarism. MRI revealed a clearly defined intrasellar mass that was heterogeneously hyperintense on T1-weighted images and markedly hypointense on T2-weighted images. We preoperatively diagnosed the patient with Rathke's cleft cyst or non-functioning pituitary adenoma. Although the tumor was completely removed using a transsphenoidal approach, the improvement of the patient's endocrine function was marginal, and continued endocrine replacement therapy was needed. Postoperatively, a histological examination revealed the tumor to be a xanthogranuloma of the intrasellar region. His visual field defects and headache improved.</p> <p>Conclusion</p> <p>Because diagnosis depends on surgical intervention and xanthogranulomas of the intrasellar region are very rare, the natural history of xanthogranuloma is still unknown. Therefore, this entity is difficult to diagnose preoperatively. We suggest that xanthogranuloma should be included in the differential diagnosis, even in the case of sellar lesions, to formulate appropriate postoperative management and improve endocrine outcomes.</p

The Role of Rab3a in Secretory Vesicle Docking Requires Association/Dissociation of Guanidine Phosphates and Munc18-1

Rab3a is a small GTPase that binds selectively to secretory vesicles and switches between active, GTP-bound and inactive, GDP-bound conformations. In yeast, Rab and SM-genes interact genetically to promote vesicle targeting/fusion. We tested different Rab3a conformations and genetic interactions with the SM-gene munc18-1 on the docking function of Rab3a in mammalian chromaffin cells. We expressed Rab3a mutants locked in the GTP- or GDP-bound form in wild-type and munc18-1 null mutant cells and analyzed secretory vesicle distribution. We confirmed that wild-type Rab3a promotes vesicle docking in wild-type cells. Unexpectedly, both GTP- and GDP-locked Rab3a mutants did not promote docking. Furthermore, wild-type Rab3a did not promote docking in munc18-1 null cells and GTP- and GDP-Rab3a both decreased the amount of docked vesicles. The results show that GTP- and GDP-locked conformations do not support a Munc18-1 dependent role of Rab3a in docking. This suggests that nucleotide cycling is required to support docking and that this action of Rab3a is upstream of Munc18-1