Lysosomal trafficking, antigen presentation, and microbial killing are controlled by the Arf-like GTPase Arl8b.

Abstract:

:Antigen presentation and microbial killing are critical arms of host defense that depend upon cargo trafficking into lysosomes. Yet, the molecular regulators of traffic into lysosomes are only partly understood. Here, using a lysosome-dependent immunological screen of a trafficking shRNA library, we identified the Arf-like GTPase Arl8b as a critical regulator of cargo delivery to lysosomes. Homotypic fusion and vacuole protein sorting (HOPS) complex members were identified as effectors of Arl8b and were dependent on Arl8b for recruitment to lysosomes, suggesting that Arl8b-HOPS plays a general role in directing traffic to lysosomes. Moreover, the formation of CD1 antigen-presenting complexes in lysosomes, their delivery to the plasma membrane, and phagosome-lysosome fusion were all markedly impaired in Arl8b silenced cells resulting in corresponding defects in T cell activation and microbial killing. Together, these results define Arl8b as a key regulator of lysosomal cellular and immunological functions.

journal_name

Immunity

journal_title

Immunity

authors

Garg S,Sharma M,Ung C,Tuli A,Barral DC,Hava DL,Veerapen N,Besra GS,Hacohen N,Brenner MB

doi

10.1016/j.immuni.2011.06.009

subject

Has Abstract

pub_date

2011-08-26 00:00:00

pages

182-93

issue

2

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(11)00267-6

journal_volume

35

pub_type

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