Clathrin light chains: arrays of protein motifs that regulate coated-vesicle dynamics

Brodsky, Frances M.; Hill, Beth; Acton, Susan; Näthke, Inke; Wong, David G.; Ponnambalam, Sreenivasan; Parham, Peter

doi:10.1016/0968-0004(91)90087-c

Cited by 87 publications

(69 citation statements)

References 37 publications

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“…Clathrin LCs are encoded by two ubiquitously expressed genes, LCa and LCb, that share ϳ60% sequence identity at the amino acid level but differ slightly in length (10). The neural isoform of LCa is composed of a series of domains, including the "conserved sequence," Hsc70-binding site, Ca 2ϩ -binding domain, HC binding site, neuron-specific insert, and a C-terminal segment that includes the calmodulin binding site (Fig.…”

Section: Calcyon Interacts With the Hc Binding Domain And C-terminal mentioning

confidence: 99%

“…The time and place of CCV assembly and breakdown are regulated by some 30 adaptor and accessory proteins (8), most of which are ubiquitous and interact with HC. In contrast to HC, only four proteins aside from HC are known to interact with LC, including calmodulin (9), Hsc70 (heat shock protein 70) (10), Hip1 (Huntingtin-interacting protein 1), and the closely related protein Hip1R (Hip1-related protein) (11)(12)(13)(14). However, targeted deletion studies indicate that neuronal enriched isoforms of several adaptor and accessory proteins are essential for optimal synaptic transmission (4).…”

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Calcyon, a Novel Partner of Clathrin Light Chain, Stimulates Clathrin-mediated Endocytosis

Xiao

Dai

Négyessy

et al. 2006

Journal of Biological Chemistry

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In the central nervous system, clathrin-mediated endocytosis is crucial for efficient synaptic transmission. Clathrin-coated vesicle assembly and disassembly is regulated by some 30 adaptor and accessory proteins, most of which interact with clathrin heavy chain. Using the calcyon cytosolic domain as bait, we isolated clathrin light chain in a yeast two-hybrid screen. The interaction domain was mapped to the heavy chain binding domain and C-terminal regions of light chain. Further, the addition of the calcyon C terminus stimulated clathrin self-assembly in a dose-dependent fashion. Calcyon, which is a single transmembrane protein predominantly expressed in brain, localized to vesicular compartments within preand postsynaptic structures. There was a high degree of overlap in the distribution of LC and calcyon in neuronal dendrites, spines, and cell bodies. Co-immunoprecipitation studies further suggested an association of calcyon with the clathrin-mediated endocytic machinery. Compared with controls, HEK293 cells overexpressing calcyon exhibited significantly enhanced transferrin uptake but equivalent levels of recycling. Conversely, transferrin uptake was largely abolished in neocortical neurons obtained from mice homozygous for a calcyon null allele, whereas recycling proceeded at wild type levels. Collectively, these data indicate a role for calcyon in clathrin-mediated endocytosis in brain.In the central nervous system, clathrin-mediated endocytosis (CME) 3 is essential for pre-and postsynaptic adaptations correlated with learning and memory (1-4). In axon terminals, CME is required for synaptic vesicle recycling, a process linked to optimizing levels of releasable pools of neurotransmitter during synaptic activity (4). Similarly, in dendritic spines, internalization of postsynaptic receptors via clathrin-coated vesicles (CCVs) plays a role in long term changes in synaptic strength (2, 5-7). The protein backbone of CCVs consists of clathrin triskelions assembled into a lattice structure. Each triskelion is composed of three heavy chains (HCs) and three light chains (LCs). The time and place of CCV assembly and breakdown are regulated by some 30 adaptor and accessory proteins (8), most of which are ubiquitous and interact with HC. In contrast to HC, only four proteins aside from HC are known to interact with LC, including calmodulin (9), Hsc70 (heat shock protein 70) (10), Hip1 (Huntingtin-interacting protein 1), and the closely related protein Hip1R (Hip1-related protein) (11-14). However, targeted deletion studies indicate that neuronal enriched isoforms of several adaptor and accessory proteins are essential for optimal synaptic transmission (4). The enrichment of Hip1 and calmodulin in neurons raises the possibility that adaptor and accessory protein interactions with LC might likewise be crucial determinants of efficient CME in the central nervous system.Calcyon is a single transmembrane protein predominantly expressed in the central nervous system and localized to membranous intracellular compartments wi...

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Section: Calcyon Interacts With the Hc Binding Domain And C-terminal mentioning

confidence: 99%

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confidence: 99%

Calcyon, a Novel Partner of Clathrin Light Chain, Stimulates Clathrin-mediated Endocytosis

Xiao

Dai

Négyessy

et al. 2006

Journal of Biological Chemistry

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“…The LC subunits suppress spontaneous lattice assembly in vitro and thus allow cellular clathrin assembly to be controlled and subjected to regulation by additional proteins (3,4). Other roles for the LCs have not yet been clearly defined, despite the fact that LCs appear to be composed of multiple functional domains (5). In this study, we establish that the function of a conserved sequence in vertebrate LCs is to bind to the CCV-enriched proteins, Hip1 and Hip1R (referred to henceforth as Hip1/R).…”

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confidence: 99%

“…These LCs are expressed in all tissues at varying relative levels (6) and are heterogeneously distributed in clathrin triskelia (7). Near the N termini of LCs there is a 22-residue sequence, shared by LCa and LCb and completely conserved in all vertebrate LCs, which is also highly conserved in LCs from non-vertebrate species (5). The first three residues of this conserved sequence are a triplet of negatively charged residues (EED) that regulate clathrin assembly (4).…”

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Huntingtin-interacting Protein 1 (Hip1) and Hip1-related Protein (Hip1R) Bind the Conserved Sequence of Clathrin Light Chains and Thereby Influence Clathrin Assembly in Vitro and Actin Distribution in Vivo

Chen

Brodsky

2005

Journal of Biological Chemistry

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Clathrin heavy and light chains form triskelia, which assemble into polyhedral coats of membrane vesicles that mediate transport for endocytosis and organelle biogenesis. Light chain subunits regulate clathrin assembly in vitro by suppressing spontaneous self-assembly of the heavy chains. The residues that play this regulatory role are at the N terminus of a conserved 22-amino acid sequence that is shared by all vertebrate light chains. Here we show that these regulatory residues and others in the conserved sequence mediate light chain interaction with Hip1 and Hip1R. These related proteins were previously found to be enriched in clathrin-coated vesicles and to promote clathrin assembly in vitro. We demonstrate Hip1R binding preference for light chains associated with clathrin heavy chain and show that Hip1R stimulation of clathrin assembly in vitro is blocked by mutations in the conserved sequence of light chains that abolish interaction with Hip1 and Hip1R. In vivo overexpression of a fragment of clathrin light chain comprising the Hip1R-binding region affected cellular actin distribution. Together these results suggest that the roles of Hip1 and Hip1R in affecting clathrin assembly and actin distribution are mediated by their interaction with the conserved sequence of clathrin light chains.

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Effect of chloroquine-induced myopathy on rat soleus muscle sarcoplasm and expression of clathrin

et al. 1998

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Clathrin light chains: arrays of protein motifs that regulate coated-vesicle dynamics

Cited by 87 publications

References 37 publications

Calcyon, a Novel Partner of Clathrin Light Chain, Stimulates Clathrin-mediated Endocytosis

Calcyon, a Novel Partner of Clathrin Light Chain, Stimulates Clathrin-mediated Endocytosis

Huntingtin-interacting Protein 1 (Hip1) and Hip1-related Protein (Hip1R) Bind the Conserved Sequence of Clathrin Light Chains and Thereby Influence Clathrin Assembly in Vitro and Actin Distribution in Vivo

Effect of chloroquine-induced myopathy on rat soleus muscle sarcoplasm and expression of clathrin

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