Early Origin of Genes Encoding Subunits of Biogenesis of Lysosome-related Organelles Complex-1, -2 and -3

Cheli, Verónica T.; Dell’Angelica, Esteban C.

doi:10.1111/j.1600-0854.2010.01044.x

Cited by 22 publications

(39 citation statements)

References 52 publications

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“…Phylogenetic analyses using the position-specific iterated BLAST (PSI-BLAST) algorithm (http://blast.ncbi.nlm.nih.gov/Blast.cgi) identified orthologs of BLOC-1 subunits (particularly BLOS1, BLOS2, and Snapin) among members of most eukaryotic supergroups (Figure S1C; Cheli and Dell’Angelica, 2010; Hayes et al, 2011). Orthologs of LOH12CR1, C17orf59, C10orf32, MEF2BNB, and KXD1 had a more limited distribution to metazoans and a few eukaryotic supergroups (Figure S1C).…”

Section: Resultsmentioning

confidence: 99%

BORC, a Multisubunit Complex that Regulates Lysosome Positioning

et al. 2015

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SUMMARY The positioning of lysosomes within the cytoplasm is emerging as a critical determinant of many lysosomal functions. Here we report the identification of a multi-subunit complex named BORC that regulates lysosome positioning. BORC comprises eight subunits, some of which are shared with the BLOC-1 complex involved in the biogenesis of lysosome-related organelles, and the others of which are products of previously uncharacterized open reading frames. BORC associates peripherally with the lysosomal membrane, where it functions to recruit the small GTPase Arl8. This initiates a chain of interactions that promotes the Kinesin-1-dependent movement of lysosomes toward the plus ends of microtubules in the peripheral cytoplasm. Interference with BORC or other components of this pathway results in collapse of the lysosomal population into the pericentriolar region. In turn, this causes reduced cell spreading and migration, highlighting the importance of BORC-dependent centrifugal transport for non-degradative functions of lysosomes.

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Section: Resultsmentioning

confidence: 99%

BORC, a Multisubunit Complex that Regulates Lysosome Positioning

et al. 2015

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“…On the other hand, there are a growing number of examples demonstrating the pervasiveness of gene loss in non-parasitic organisms. Loss of ancestral features of the eukaryotic ES has accompanied, for example, evolution of the fungal kingdom, particularly the yeast lineage including S. cerevisiae ( Figure 2); components of the ES secondarily missing in the budding yeast due to losses at different points of the fungal evolutionary history include, for example, the adaptin complex AP4, the BBSome coat complex, several paralogs of the RAB family, at least one ArfGEF and ArfGAP, several RabGAP proteins, the Golgi-associated ARL5 GTPase, the EHD/ RME-1 family, or subunits of the BLOC-1, BLOC-2 and BLOC3 complexes implicated in biogenesis of lysosomes-related organelles (Boehm and Bonifacino 2001, Pereira-Leal 2008, Cheli and Dell'Angelica 2010, Hodges et al 2010. Such reductions have also occurred throughout Metazoa, as exemplified, for example, by the absence of the AP4 adaptin complex and the endocytic protein Eps15 in C. elegans and D. melanogaster (Boehm andBonifacino 2001, Field et al 2007), by numerous losses of different SNARE proteins in many metazoan lineages (Kloepper et al 2008), or by the loss of the Sec2 RabGEF from dipteran insects (Elias 2008).…”

Section: The Omnipresent Reductive Evolutionmentioning

confidence: 99%

Patterns and processes in the evolution of the eukaryotic endomembrane system

Eliáš

2010

Molecular Membrane Biology

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The eukaryotic endomembrane system (ES) is served by hundreds of dedicated proteins. Experimental characterization of the ES-associated molecular machinery in several model eukaryotes complemented by a recent progress in phylogenomics and comparative genomics have revealed a conserved complex core of the machinery that appears to have been established before the last eukaryotic common ancestor (LECA). At the same time, modern eukaryotes exhibit a huge variation in the ES resulting from a multitude of evolutionary processes operating along the ever-branching paths from the LECA to its descendants. The most important source of evolutionary novelty in the ES functioning has undoubtedly been gene duplication followed by divergence of the gene copies, responsible not only for the pre-LECA establishment of many multi-paralog families of proteins in the very core of the ES-associated machinery, but also for post-LECA lineage-specific elaborations via family expansions and the origin of novel components. Extreme sequence divergence has obscured actual homologous relationships between potentially many components of the machinery, even between orthologous proteins, as illustrated by the yeast Vps51 subunit of the vesicle tethering complex GARP hypothesized here to be a highly modified ortholog of a conserved eukaryotic family typified by the zebrafish Fat-free (Ffr) protein. A dynamic evolution of many ES-associated proteins, especially those centred around RAB and ARF GTPases, seems to take place at the level of their domain architectures. Finally, reductive evolution and recurrent gene loss are emerging as pervasive factors shaping the ES in all phylogenetic lineages.Key to a full understanding of evolution of the ES, like of any other aspect of the eukaryotic cell, is a robust phylogenetic scheme bringing an order into the vast

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“…The majority of the HPS-affected genes encode subunits of BLOC-1, -2 and -3, which are well-conserved in metazoans; distant homologues of BLOC-1 and BLOC-3 can be found in Dictyostelium and S. cerevisiae (24, 70). Each complex is an obligate oligomer, such that most subunits of the corresponding BLOC are destabilized by known HPS-associated mutations in one BLOC subunit.…”

Section: Hps-associated Multisubunit Complexesmentioning

confidence: 99%