Abstract：
:Sorting endosomes (SEs) are the regulatory hubs for sorting cargo to multiple organelles, including lysosome-related organelles, such as melanosomes in melanocytes. In parallel, melanosome biogenesis is initiated from SEs with the processing and sequential transport of melanocyte-specific proteins toward maturing melanosomes. However, the mechanism of cargo segregation on SEs is largely unknown. Here, RNAi screening in melanocytes revealed that knockdown of Rab4A results in defective melanosome maturation. Rab4A-depletion increases the number of vacuolar endosomes and disturbs the cargo sorting, which in turn lead to the mislocalization of melanosomal proteins to lysosomes, cell surface and exosomes. Rab4A localizes to the SEs and forms an endosomal complex with the adaptor AP-3, the effector rabenosyn-5 and the motor KIF3, which possibly coordinates cargo segregation on SEs. Consistent with this, inactivation of rabenosyn-5, KIF3A or KIF3B phenocopied the defects observed in Rab4A-knockdown melanocytes. Further, rabenosyn-5 was found to associate with rabaptin-5 or Rabip4/4' (isoforms encoded by Rufy1) and differentially regulate cargo sorting from SEs. Thus, Rab4A acts a key regulator of cargo segregation on SEs.This article has an associated First Person interview with the first author of the paper.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Nag S,Rani S,Mahanty S,Bissig C,Arora P,Azevedo C,Saiardi A,van der Sluijs P,Delevoye C,van Niel G,Raposo G,Setty SRGdoi
10.1242/jcs.216226subject
Has Abstractpub_date
2018-09-20 00:00:00issue
18eissn
0021-9533issn
1477-9137pii
jcs.216226journal_volume
131pub_type
杂志文章abstract：:Aminopeptidase N purified from whole Manduca sexta midgut binds the Cry1Ac insecticidal toxin from Bacillus thuringiensis and this binding is inhibited by N-acetylgalactosamine (GalNAc). We have examined the membrane permeabilising activity of the Cry1Ac toxin using brush border membrane vesicles (BBMV) prepared from ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:A fundamental prediction of the hypothesis that critical events in tumour formation are rare is that the tumours develop by clonal expansion. This prediction has been tested by establishing the isozyme content of tumours induced in mosaic animals whose normal tissues contain two distinguishable isozyme activities. The...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:The molecular motor dynein is essential for mitotic spindle orientation, which defines the axis of cell division. The light intermediate chain subunits, LIC1 and LIC2, define biochemically and functionally distinct vertebrate dynein complexes, with LIC2-dynein playing a crucial role in ensuring spindle orientation. We...
journal_title：Journal of cell science
pub_type： 杂志文章
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abstract：:Borrelia burgdorferi is the causative agent of Lyme disease, a multisystemic disorder affecting primarily skin, joints and nervous system. Successful internalization and intracellular processing of borreliae by immune cells like macrophages is decisive for the outcome of a respective infection. Here, we use for the fi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.252320
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abstract：:Nerve branching is controlled by intrinsic and extrinsic cues, one of which may be a small applied electric field. Lateral processes were induced by passing current through a micropipette placed at 90 degrees to the shaft of a developing nerve. The appearance of processes was a polarised event with a large majority ar...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:In this paper, we identify the chondroitin sulfate proteoglycan versican V2 as a major inhibitor of axonal growth in the extracellular matrix of the mature central nervous system. In immunohistochemical and in situ hybridization experiments we show that this tissue-specific splice variant of versican is predominantly ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：:Madin-Darby canine kidney cells (MDCK) were transfected with a cDNA encoding the glycosyl-phosphatidylinositol (GPI)-anchored protein mouse Thy-1 in order to study the steady-state surface distribution of exogenous and endogenous GPI-linked proteins. Immunofluorescence of transfected cells grown on collagen-coated cov...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.044255
更新日期：2009-05-01 00:00:00
abstract：:In a wild population of the American newt Notophthalmus viridescens 15 females out of a total of 94 were found to be heterozygous for a paracentric inversion which includes almost the whole of the longer arm of the smallest chromosome (XI). The inversion was recognized in preparations of lampbrush chromosomes because ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-04-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1242/jcs.051755
更新日期：2009-11-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.072876
更新日期：2010-10-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.014878
更新日期：2008-03-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章,评审
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更新日期：2018-04-09 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:The nature, kinetics and cofactor requirements of leukocyte adhesion to cultured vascular cells have been investigated in vitro, using a model system in which leukocyte suspensions are in continuous motion over the cultured cells. Adhesion is assessed by histological examination or by using 51Cr-labelled leukocytes. L...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-10-01 00:00:00
abstract：:Ryanodine receptors (RyRs) are expressed on the endoplasmic reticulum of many cells, where they form intracellular Ca2+-release channels that participate in the generation of intracellular Ca2+ signals. Here we report studies on the intracellular localisation and functional properties of transfected RyR1 or RyR3 chann...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-06-15 00:00:00
abstract：:A myosin heavy chain polypeptide has been identified and localized in Nicotiana pollen tubes using monoclonal anti-myosin antibodies. The epitopes of these antibodies were found to reside on the myosin heavy chain head and rod portion and were, therefore, designated anti-S-1 (myosin S-1) and anti-LMM (light meromyosin...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Microtubules stimulate contractile-ring formation in the equatorial cortex and simultaneously suppress contractility in the polar cortex; how they accomplish these differing activities is incompletely understood. We measured the behavior of GFP-actin in mammalian cells treated with nocodazole under conditions that eit...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.027052
更新日期：2008-07-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1985-03-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
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journal_title：Journal of cell science
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doi：10.1242/jcs.03415
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pub_type： 杂志文章
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-12-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:Removal of interleukin-3 from murine IC.DP pre-mast cells results in irreversible commitment to apoptosis within 18 hours. To identify early events necessary for the engagement of apoptosis we examined the regulation of intracellular pH (pH(i)). IC.DP cells acidified 2 hours after removal of interleukin-3 (before disc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:We have cloned and characterized a single copy C. reinhardtii gene containing an open reading frame of 333 nucleotides encoding a 12.7 kDa protein. The novel protein, DIP13, exhibits 60% identity with two mammalian proteins, human NA14 and an unnamed mouse protein. Homologous sequences are also present in several prot...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00337
更新日期：2003-04-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
