RAB26 coordinates lysosome traffic and mitochondrial localization

Ramon U. Jin, Jason C. Mills

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

As they mature, professional secretory cells like pancreatic acinar and gastric chief cells induce the transcription factor MIST1 (also known as BHLHA15) to substantially scale up production of large secretory granules in a process that involves expansion of apical cytoplasm and redistribution of lysosomes and mitochondria. How a scaling factor like MIST1 rearranges cellular architecture simply by regulating expression levels of its transcriptional targets is unknown. RAB26 is a MIST1 target whose role in MIST1-mediated secretory cell maturation is also unknown. Here, we confirm that RAB26 expression, unlike most Rabs which are ubiquitously expressed, is tissue specific and largely confined to MIST1-expressing secretory tissues. Surprisingly, functional studies showed that RAB26 predominantly associated with LAMP1/cathepsin D lysosomes and not directly with secretory granules. Moreover, increasing RAB26 expression -by inducing differentiation of zymogensecreting cells or by direct transfection -caused lysosomes to coalesce in a central, perinuclear region. Lysosome clustering in turn caused redistribution of mitochondria into distinct subcellular neighborhoods. The data elucidate a novel function for RAB26 and suggest a mechanism for how cells could increase transcription of key effectors to reorganize subcellular compartments during differentiation.

Original languageEnglish
Pages (from-to)1018-1032
Number of pages15
JournalJournal of cell science
Volume127
Issue number5
DOIs
StatePublished - Mar 2014

Keywords

  • LAMP1
  • MIST1
  • Vesicle trafficking
  • Zymogenic cell

Fingerprint

Dive into the research topics of 'RAB26 coordinates lysosome traffic and mitochondrial localization'. Together they form a unique fingerprint.

Cite this