Sterol Carrier Protein-2, a Nonspecific Lipid-Transfer Protein, in Intracellular Cholesterol Trafficking in Testicular Leydig Cells

Abstract

Sterol carrier protein-2 (SCP2), also called nonspecific lipid-transfer protein, is thought to play a major role in intracellular lipid transport and metabolism, and it has been associated with diseases involving abnormalities in lipid trafficking, such as Zellweger syndrome. The Scp2 gene encodes the 58 kDa sterol carrier protein-x (SCPX) and 15 kDa pro-SCP2 proteins, both of which contain a 13 kDa SCP2 domain in their C-termini. We found that 22-NBD-cholesterol, a fluorescent analog of cholesterol and a preferred SCP2 ligands, was not localized in the peroxisomes. This raises questions about previous reports on the localization of the SCPX and SCP2 proteins and their relationship to peroxisomes and mitochondria in intracellular cholesterol transport. Immunofluorescent staining of cryosections of mouse testis and of MA-10 mouse tumor Leydig cells showed that SCPX and SCP2 are present in both mouse testicular interstitial tissue and in MA-10 cells. Fluorescent fusion proteins of SCPX and SCP2, as well as confocal live-cell imaging, were used to investigate the subcellular targeting of these proteins and the function of the putative mitochondrial targeting sequence. The results showed that SCPX and SCP2 are targeted to the peroxisomes by the C-terminal PTS1 domain, but the putative N-terminal mitochondrial targeting sequence alone is not potent enough to localize SCPX and SCP2 to the mitochondria. Homology modeling and molecular docking studies indicated that the SCP2 domain binds cholesterol, but lacks specificity of the binding and/or transport. These findings further our understanding of the role of SCPX and SCP2 in intracellular cholesterol transport, and present a new point of view on the role of these proteins in cholesterol trafficking.

Complementary transcriptomic and proteomic analyses reveal regulatory mechanisms of milk protein production in dairy cows consuming different forages

“…Increased SCD5 transcript also suggests enhanced fatty acid metabolism in mammary glands of the RS group. Sterol carrier protein-2 (SCP2), also called nonspecific lipid-transfer protein, is thought to be important in intracellular lipid trafficking and metabolism 34 , such as transporting cholesterol from intracellular sites (lipid droplets) to the mitochondria 35 . The protein SCP2 increased in abundance, indicating a higher level of fatty acid transport in the RS group.…”

LINC00261 elevation inhibits angiogenesis and cell cycle progression of pancreatic cancer cells by upregulating SCP2 via targeting FOXP3

“… 38 Importantly, SCP2 may be especially associated with diseases involving abnormalities in lipid trafficking. 39 As is widely appreciated, PC is aggressive with dismal prognosis due to its propensity for widespread metastatic disease. 40 In addition, several research projects have reported an increased de novo lipogenesis in PC cells.…”

Larvicidal Activity of Lantana Indica and Vitex Negundo on Culex Quinquefasciatus

“…Although the presence of hydrogen in DEET stabilizes the acetylcholine interaction, the higher docking energy of Tangeretin-1 suggest that the Van der Waal forces play a more crucial role in stabilizing the docked complex and can explain the mechanism involved in mortality of mosquito larvae when exposed to crude extracts. A similar docking approach was given to Sterol binding protein-2, where tangeritin-1 showed the least docking energy [18]. The interacting residues are THR35, THR65, ASP88, LYS89, MET90, GLU91, and VAL92 all amino acids contributed to Van der Waal interactions as compared to DEET binding which also had Van der Waal interactions contributing to the stability of the complex.…”