Identification of transmembrane domains that regulate spatial arrangements and activity of prokineticin receptor 2 dimers.

The chemokine prokineticin 2 (PK2) activates its cognate G protein-coupled receptor (GPCR) PKR2 to elicit various downstream signaling pathways involved in diverse biological processes. Many GPCRs undergo dimerization that can modulate a number of functions including membrane delivery and signal transduction. The aim of this study was to elucidate the interface of PKR2 protomers within dimers by analyzing the ability of PKR2 transmembrane (TM) deletion mutants to associate with wild type (WT) PKR2 in yeast using co-immunoprecipitation and mammalian cells using bioluminescence resonance energy transfer. Deletion of TMs 5-7 resulted in a lack of detectable association with WT PKR2, but could associate with a truncated mutant lacking TMs 6-7 (TM1-5). Interestingly, TM1-5 modulated the distance, or organization, between protomers and positively regulated Gαs signaling and surface expression of WT PKR2. We propose that PKR2 protomers form type II dimers involving TMs 4 and 5, with a role for TM5 in modulation of PKR2 function.

Spontaneous temporal cerebrospinal fluid leak. A case report and literature review.

An abnormal communication between the subarachnoid spaces and the tympanic cavity and mastoid cells can determine a cerebrospinal fluid (CSF) leak in the air spaces of the temporal bone. The etiology of CFS leak in the temporal air cells includes acquired, congenital and spontaneous causes. Spontaneous CSF leak, defined as a leak without a manifest cause, is present in about 4% of cases and often occurs in the middle cranial fossa. We describe a case of spontaneous CSF leak in the right temporal air cells that mimicked a skull fracture in a subject with headache and apparent rhinorrhea after a head trauma. Both CT and MRI play a key role in the differential diagnosis between post-traumatic temporal CSF leak due to a fracture and spontaneous leak: traumatic CSF leak often does not require a surgical approach, whereas spontaneous CSF leak may need surgical treatment because of the risk of meningitis.

Vertebral aggressive hemangioma. A case report and literature review.

Aggressive hemangiomas are rare and can compress the spinal cord, nerve roots or both, producing myelopathy or radiculopathy. This report describes an aggressive and compressive hemangioma of the body of the Th9 vertebra in a woman with symptoms of medullary sufferance, treated with embolization of the afferent vessels of the lesion followed by radiotherapy.

The specificity of binding of glycoprotein hormones to their receptors.

The glycoprotein hormone receptor family is peculiar because, in contrast to other G protein-coupled receptors, a large N-terminal extracellular ectodomain is responsible for hormone recognition. Hormone-receptor pairs have evolved in such a manner that a limited number of positions both at the 'seat-belt' domain of the hormone and the leucine-rich repeats of the receptor, play attractive and repulsive interactions for binding and specificity, respectively. Surprisingly, the constitutive activity of the receptor, mostly modulated by highly conserved amino acids within the heptahelical domain of the receptor (i.e., outside the hormone binding region), also regulates effectiveness of hormone recognition by the extracellular part. In this review we analyze, at the molecular level, these important discriminating determinants for selective binding of glycoprotein hormones to their receptors, as well as natural mutations, observed in patients with gestational hyperthyroidism or ovarian hyperstimulation syndrome, that modify the selectivity of binding.