Cofilin recruits F-actin to SPCA1 and promotes Ca2+-mediated secretory cargo sorting.

The actin filament severing protein cofilin-1 (CFL-1) is required for actin and P-type ATPase secretory pathway calcium ATPase (SPCA)-dependent sorting of secretory proteins at the trans-Golgi network (TGN). How these proteins interact and activate the pump to facilitate cargo sorting, however, is not known. We used purified proteins to assess interaction of the cytoplasmic domains of SPCA1 with actin and CFL-1.

Secretory cargo sorting at the trans-Golgi network.

Sorting of proteins for secretion from cells is crucial for normal physiology and the regulation of key cellular events. Although the sorting of lysosomal hydrolases at the trans-Golgi network (TGN) for delivery to pre-lysosomes is well characterized, the corresponding mechanism by which secreted proteins are sorted for plasma-membrane delivery remains poorly understood. Recent discoveries have revealed a novel sorting mechanism that requires the linkage between the cytoplasmic actin cytoskeleton to the membrane-anchored Ca(2+) ATPase, SPCA1 (secretory pathway calcium ATPase 1), and the luminal 45 kDa Ca(2+)-binding protein, Cab45, for successful sorting of a subset of proteins at the TGN.

Cab45 is required for Ca(2+)-dependent secretory cargo sorting at the trans-Golgi network.

Ca(2+) import into the lumen of the trans-Golgi network (TGN) by the secretory pathway calcium ATPase1 (SPCA1) is required for the sorting of secretory cargo. How is Ca(2+) retained in the lumen of the Golgi, and what is its role in cargo sorting? We show here that a soluble, lumenal Golgi resident protein, Cab45, is required for SPCA1-dependent Ca(2+) import into the TGN; it binds secretory cargo in a Ca(2+)-dependent reaction and is required for its sorting at the TGN.

PKD controls mitotic Golgi complex fragmentation through a Raf-MEK1 pathway.

Before entering mitosis, the stacks of the Golgi cisternae are separated from each other, and inhibiting this process delays entry of mammalian cells into mitosis. Protein kinase D (PKD) is known to be involved in Golgi-to-cell surface transport by controlling the biogenesis of specific transport carriers. Here we show that depletion of PKD1 and PKD2 proteins from HeLa cells by small interfering RNA leads to the accumulation of cells in the G2 phase of the cell cycle and prevents cells from entering mitosis.

Protein kinase D controls voluntary-running-induced skeletal muscle remodelling.

Skeletal muscle responds to exercise by activation of signalling pathways that co-ordinate gene expression to sustain muscle performance. MEF2 (myocyte enhancer factor 2)-dependent transcriptional activation of MHC (myosin heavy chain) genes promotes the transformation from fast-twitch into slow-twitch fibres, with MEF2 activity being tightly regulated by interaction with class IIa HDACs (histone deacetylases). PKD (protein kinase D) is known to directly phosphorylate skeletal muscle class IIa HDACs, mediating their nuclear export and thus derepression of MEF2.

Large proportion of low frequency microsatellite-instability and loss of heterozygosity in pheochromocytoma and endocrine tumors detected with an extended marker panel.

Purpose: Pheochromocytoma (PCC) is a usually benign tumor originated in the majority of patients from the adrenal medulla. Regarding sporadic forms of PCC, mechanisms of pathogenesis are largely unknown. Recently, microsatellite-instability (MSI) was discussed as genetic factor contributing to PCC development.