Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular membrane fusion is conserved from yeast to man as well as among different intracellular trafficking pathways. This process can be generally divided into several well-defined biochemical reactions. First, an early recognition (or tethering) takes place between donor and acceptor membranes, mediated by ypt/rab GTPases and complexes of tethering factors. Subsequently, a closer association between the two membranes is achieved by a docking process, which involves tight association between membrane proteins termed SNAREs. The formation of such a trans-SNARE complex leads to the final membrane fusion, resulting in an accumulation of cis-SNARE complexes on the acceptor membrane. Thus, multiple rounds of transport and delivery of the donor SNARE back to its original membrane require dissociation of the SNARE complexes. SNARE dissociation, termed priming, is mediated by the AAA ATPase, N-ethylmaleimide-sensitive factor (NSF) and its partner, soluble NSF attachment protein (SNAP), in a reaction that requires ATP hydrolysis. In the present review we focus on LMA1 and GATE-16, two low-molecular-weight proteins, which assist in priming SNARE molecules in the vacuole in yeast and the Golgi complex in mammals, respectively. LMA1 and GATE-16 are suggested to keep the dissociated cis-SNAREs apart from each other, allowing multiple fusion processes to take place. GATE-16 belongs to a novel family of ubiquitin-like proteins conserved from yeast to man. We discuss here the involvement of this family in multiple intracellular trafficking pathways.
 ...
PMID:Involvement of LMA1 and GATE-16 family members in intracellular membrane dynamics. 1291 55

The hexameric ATPase, N-ethylmaleimide sensitive factor (NSF), is essential to vesicular transport and membrane fusion because it affects the conformations and associations of the soluble NSF attachment protein receptor (SNARE) proteins. NSF binds SNAREs through adaptors called soluble NSF attachment proteins (alpha- or beta-SNAP) and disassembles SNARE complexes to recycle the monomers. NSF contains three domains, two nucleotide-binding domains (NSF-D1 and -D2) and an amino terminal domain (NSF-N) that is required for SNAP-SNARE complex binding. Mutagenesis studies indicate that a cleft between the two sub-domains of NSF-N is critical for binding. The structural conservation of N domains in NSF, p97/VCP, and VAT suggests that a similar type of binding site could mediate substrate recognition by other AAA proteins. In addition to SNAP-SNARE complexes, NSF also binds other proteins and protein complexes such as AMPA receptor subunits (GluR2), beta2-adrenergic receptor, beta-Arrestin1, GATE-16, LMA1, rabs, and rab-containing complexes. The potential for these interactions indicates a broader role for NSF in the assembly/disassembly cycles of several cellular complexes and suggests that NSF may have specific regulatory effects on the functions of the proteins involved in these complexes. The structural requirements for these interactions and their physiological significance will be discussed.
 ...
PMID:Multiple binding proteins suggest diverse functions for the N-ethylmaleimide sensitive factor. 1503 35

The Golgi apparatus in animal cells breaks down at the onset of mitosis and is later rebuilt in the two daughter cells. Two AAA ATPases, NSF and p97/VCP, have been implicated in regulating membrane fusion steps that lead to regrowth of Golgi cisternae from mitotic fragments. NSF dissociates complexes of SNARE proteins, thereby reactivating them to mediate membrane fusion. However, NSF has a second function in regulating SNARE pairing together with the ubiquitin-like protein GATE-16. p97/VCP, on the other hand, is involved in a cycle of ubiquitination and deubiquitination of an unknown target that governs Golgi membrane dynamics. Here, these findings are reviewed and discussed in the context of the increasingly evident role of ubiquitin in membrane traffic processes.
 ...
PMID:Golgi reassembly after mitosis: the AAA family meets the ubiquitin family. 1603 55

The Golgi apparatus in animal cells breaks down at the onset of mitosis and is later rebuilt in the two daughter cells. Two AAA ATPases, NSF and p97/VCP, have been implicated in regulating membrane fusion steps that lead to regrowth of Golgi cisternae from mitotic fragments. NSF dissociates complexes of SNARE proteins, thereby reactivating them to mediate membrane fusion. However, NSF has a second function in regulating SNARE pairing together with the ubiquitin-like protein GATE-16. p97/VCP, on the other hand, is involved in a cycle of ubiquitination and deubiquitination of an unknown target that governs Golgi membrane dynamics. Here, these findings are reviewed and discussed in the context of the increasingly evident role of ubiquitin in membrane traffic processes.
 ...
PMID:Golgi reassembly after mitosis: the AAA family meets the ubiquitin family. 1587 10