Post-translationally modified peptides are involved in many aspects of plant growth and development. The maturation of these peptides from their larger precursors is still poorly understood. We show here that the biogenesis of CLEL6 and CLEL9 peptides in Arabidopsis thaliana requires a series of processing events in consecutive compartments of the secretory pathway. Following cleavage of the signal peptide upon entry into the endoplasmic reticulum (ER), the peptide precursors are processed in the cis-Golgi by the subtilase SBT6.1. SBT6.1-mediated cleavage within the variable domain allows for continued passage of the partially processed precursors through the secretory pathway, and for subsequent post-translational modifications including tyrosine sulfation and proline hydroxylation within, and proteolytic maturation after exit from the Golgi. Activation by subtilases including SBT3.8 in post-Golgi compartments depends on the N-terminal aspartate of the mature peptides. Our work highlights the complexity of post-translational precursor maturation allowing for stringent control of peptide biogenesis.

Hypervitaminosis D in cats has been reported from ingestion of vitamin D 3 -containing rodenticide and pet food. Affected animals present with lethargy, chronic weight loss, anorexia, polyuria, episodic vomiting and signs of respiratory disturbance, such as cough and difficulty in breathing. Laboratory changes in cats with hypervitaminosis D included hypercalcaemia, hyperphosphataemia, alkalosis, high urea and creatinine concentrations, hypercalciuria and a decrease in urine concentrating ability. 1-4 Case descriptionsA 6-month-old sexually intact male British Shorthair cat (cat 1) weighing 2.5 kg presented to the Veterinary Teaching Hospital of the Ludwig Maximilian University of Munich for a 3-week history of polyuria, lethargy and laboured breathing breathing. The cat's littermate (2.3 kg sexuallyintact female -cat 2) also living in their household, showed similar, but less severe, signs. One year previously, a sibling of the two cats (cat 3) (same parents, but from a previous litter) had been presented by the same owners because of similar, yet more severe, clinical signs (polyuria, polydipsia, lethargy, anorexia, coughing for 3 months) at the age of 5 months. This cat had been euthanased owing to his overall bad condition, poor prognosis and financial constraints after the initial diagnostic evaluation had revealed renal failure with marked renal azotaemia, metabolic acidosis, hyperphosphataemia, marked anaemia and severe hypercalcaemia, as well as severe radiographic lung changes characterised by a generalised bronchointerstitial pattern and peribronchial cuffing.On physical examination cat 1 was lethargic and moderately dehydrated. It showed polypnoea with AbstractTwo siblings, a 6-month-old sexually intact male weighing 2.5 kg (cat 1) and a sexually intact female (cat 2) British Shorthair cat weighing 2.3 kg, were examined because of a 3-week history of polyuria, lethargy and laboured breathing. One year previously, another sibling (cat 3) had been presented because of similar, yet more severe, clinical signs at the age of 5 months. Physical examination revealed lethargy, dehydration and polypnoea with slightly increased inspiratory effort. Diagnostic investigation revealed severe hypercalcaemia (cats 1-3), renal azotaemia (cats 1 and 3) and a radiologically generalised miliary interstitial pattern of the lungs (cats 1-3) attributable to hypervitaminosis D caused by ingestion of commercial cat food. Cat 3 was euthanased. Cats 1 and 2 were treated with isotonic saline solution (180 ml/kg IV daily), sucralfate (30 mg/kg PO q12h), terbutaline (only cat 1: 0.1 mg/kg SC q4h), furosemide (1.5 mg/kg IV q8h) and tapering doses of prednisolone. Cat 2 was normal on day 14. Cat 1 had stable renal disease and was followed up to day 672. The radiological generalised military interstitial pattern of the lungs had improved markedly. Excessive cholecalciferol-containing commercially available cat food poses a great hazard to cats. Supportive treatment may result in long-term survival and improvement of radiological pul...

AbstractPost-translationally modified peptides are involved in many aspects of plant growth and development. The maturation of these peptides from their larger precursors is still poorly understood. We show here that the biogenesis of CLEL6 and CLEL9 peptides in Arabidopsis thaliana requires a series of processing events in consecutive compartments of the secretory pathway. Following cleavage of the signal peptide upon entry into the endoplasmic reticulum (ER), the peptide precursors are processed in the cis-Golgi by the subtilase SBT6.1. SBT6.1-mediated cleavage within the variable domain allows for continued passage of the partially processed precursors through the secretory pathway, and is a prerequisite for subsequent post-translational modifications including tyrosine sulfation and proline hydroxylation within, and proteolytic maturation after exit from the Golgi. Activation by subtilase SBT3.8 in post-Golgi compartments depends on the N-terminal aspartate of the mature peptides. Our work highlights the complexity of post-translational precursor maturation allowing for stringent control of peptide biogenesis.

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