Clathrin is required for postmitotic Golgi reassembly

Abstract

During the G2-M transition, the highly organized Golgi apparatus undergoes reversible fragmentation through unstacking of the cisternal ribbon and disassembly into radially dispersed vesicles and tubules. These Golgi-derived fragments redistribute randomly within the cytoplasm, partition stochastically, and in telophase coalesce to generate a functionally and structurally intact Golgi complex. Here we identified a novel step in postmitotic Golgi reassembly that requires the clathrin heavy chain (CHC). We used siRNA-mediated CHC knockdown, biochemistry, and morphological analysis and showed that the spindle- and spindle pole-associated clathrin pools are membrane-bound and required for postmitotic Golgi reassembly. The results presented here show that clathrin remains associated with the spindle poles throughout mitosis and that this clathrin pool is distinct from the previously characterized spindle-associated population. We suggest that clathrin may provide a template for postmitotic Golgi reassembly and cisternal remodeling. In absence of the CHC, the Golgi apparatus remained disconnected and disordered and failed to regain its characteristic perinuclear, lace-like morphology. Our findings build on previous independent reports that clathrin is required for Golgi reassembly following disruption with pharmacological agents and for mitotic chromosome congression.

The Role of Clathrin in Post-Golgi Trafficking in Toxoplasma gondii

“…Furthermore, like in other eukaryotes CHC1 appears to be involved in segregation of the Golgi during mitosis [36]. …”

“…Over the last 50 years a growing number of functional studies have reported evidence for its impact on diverse physiologically processes besides its role in endocytic and secretory membrane transport, such as cytokinesis [8,39,40], Golgi integrity [36], secretory granule biogenesis [41], and mitotic and meiotic spindle organisation and stabilisation [42,43]. Without exception clathrin localisation was always correlated with its site of action in these reports.…”

Diversity of Clathrin Function: New Tricks for an Old Protein

“…There are multiple well-defined roles for clathrin in the TGN, ranging from sorting lysosomal enzymes to contributing to maturation of secretory granules by removal of constitutively expressed proteins (Figure 1) (Brodsky et al 2001 after drug-induced fragmentation (Radulescu et al 2007) and fragmentation during mitosis (Radulescu & Shields 2012). This may be the result of a requirement for clathrin-mediated membrane traffic to deliver needed proteins that mediate Golgi-stack fusion.…”

Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction

“…Both dystonin-a2 and MACF1b have been found in the Golgi apparatus, and overexpressed dystonin-a2 colocalizes with the cis -Golgi protein GM130, suggesting a functional role in Golgi apparatus-mediated MT nucleation [ 119 , 136 , 142 ]. Other MT-associated proteins, such as MAP1B and clathrin, have been shown to promote MT polymerization and stability when localized to the Golgi apparatus [ 143 , 144 ]. Dystonin-a2 has been shown to interact with both MAP1B and clathrin via the modular plakin domain [ 145 ].…”