Protein translocation: Rehearsing the ABCs

نویسندگان

Ann E Cleves

Regis B Kelly

چکیده

Signal-mediated translocation of proteins occurs across the membranes of several organelles, including the endoplasmic reticulum (ER), peroxisomes, mitochondria and lysosomes. In some cases, signal-mediated translocation involves a well-characterized molecular machine — or translocon — such as the Sec61 complex in the ER. In parallel with these systems, several membranes also have members of the ATP-binding-cassette (ABC) protein family (Fig. 1), transporters that are capable of translocating a variety of substrates across membranes, including peptides and proteins [1]. The recent discovery that some enzymes are translocated directly from the cytoplasm into the vacuole in yeast [2,3] prompts a reexamination of these alternative routes of transport that do not use the conventional signal-peptide-mediated mechanisms. Transport across organelle membranes The molecular machinery responsible for signal-mediated protein translocation across the ER membrane is well known [4]. In addition to this ‘classical’ translocation machinery, the ER also contains the TAP1–TAP2 (transporter associated with antigen presentation) heterodimer that transports peptides from the cytosol into the ER lumen, in an ATP-dependent manner. There, the peptides assemble with class I major histocompatibility complex (MHC) molecules for presentation to cells of the immune system [5]. TAP1 and TAP2 are members of the ABC family and are each a ‘half transporter’, consisting of a membrane-spanning domain (with six transmembrane regions) and an ATP-binding domain. Expression of TAP1 and TAP2 in insect cells showed that the TAP1–TAP2 complex requires no additional cofactors to function as a peptide transporter [6]. The TAP complex acts as a selective peptide pump, because human, rat and mouse TAP1–TAP2 complexes have been shown to display some specificity for peptide substrates [7].

متن کامل

منابع مشابه

Fusion Oncogenes in Aneurysmal Bone Cyst USP6 (Tre2)

Aneurysmal bone cyst (ABC) is a locally aggressive osseous lesion that typically occurs during the first two decades of life. ABC was regarded historically as a nonneoplastic process, but recent cytogenetic data have shown clonal rearrangements of chromosomal bands 16q22 and 17p13, indicating a neoplastic basis in at least some ABCs. Herein we show that a recurring ABC chromosomal translocation...

متن کامل

USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst.

متن کامل

Intercellular Trafficking of VP22, a Herpes Simplex Virus Type 1 Tegument Protein

The herpes simplex virus type 1 (HSV-1) tegument protein, VP22 has been reported to have the property of intercellular transport. The previous studies have shown that following expression of a fusion protein containing VP22 it spreads to every cell in a monolayer and concentrates in the nucleus. In spite of these reports, some studies have shown that VP22 trafficking and its nucleus accumulatio...

متن کامل

Human tau becomes phosphorylated and forms filamentous deposits when overexpressed in lamprey central neurons in situ.

Microinjection of plasmids encoding human tau (htau) protein into identified lamprey reticulospinal neurons (anterior bulbar cells, or ABCs) in situ induces chronic htau expression. htau protein is transported to both the axon and dendrites of expressing ABCs by mechanisms that require the C-terminal domain of htau protein but do not require directed htau mRNA transport. htau becomes phosphoryl...

متن کامل