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J Cell Sci ; 135(5)2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33912962


Membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and late endosomes/lysosomes (LE/lys) are emerging as critical hubs for diverse cellular events, and changes in their extents are linked to severe neurological diseases. While recent studies show that the synaptotagmin-like mitochondrial-lipid-binding (SMP) domain-containing protein PDZD8 may mediate the formation of ER-LE/lys MCSs, the cellular functions of PDZD8 remain largely elusive. Here, we attempt to investigate the lipid transfer activities of PDZD8 and the extent to which its cellular functions depend on its lipid transfer activities. In accordance with recent studies, we demonstrate that PDZD8 is a protrudin (ZFYVE27)-interacting protein and that PDZD8 acts as a tether at ER-LE/lys MCSs. Furthermore, we discover that the SMP domain of PDZD8 binds glycerophospholipids and ceramides both in vivo and in vitro, and that the SMP domain can transport lipids between membranes in vitro. Functionally, PDZD8 is required for LE/lys positioning and neurite outgrowth, which is dependent on the lipid transfer activity of the SMP domain.

Acta Crystallogr Sect E Struct Rep Online ; 64(Pt 8): o1611, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-21203304


The mol-ecule of the title compound, C(18)H(17)N(7)S, is non-planar, with a dihedral angle of 71.4 (4)° between the two triazole rings, and an angle of 15.5 (3)° between the two phenyl rings. An intra-molecular N-H⋯S hydrogen bond forms a five-membered ring.

Acta Crystallogr Sect E Struct Rep Online ; 64(Pt 8): o1612, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-21203305


In the title mol-ecule, C(17)H(16)N(4)O, the triazole ring makes dihedral angles of 29.00 (1) and 77.74 (1)°, respectively, with the phenyl and benzene rings. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into chains extending along the c axis.