Structures of C1q-like Proteins Reveal Unique Features among the C1q/TNF Superfamily
STRUCTURE
Authors: Ressl, Susanne; Vu, Brandon K.; Vivona, Sandro; Martinelli, David C.; Suedhof, Thomas C.; Brunger, Axel T.
Abstract
C1q-like (C1QL) -1, -2, and -3 proteins are encoded by homologous genes that are highly expressed in brain. C1QLs bind to brain-specific angiogenesis inhibitor 3 (BAI3), an adhesion-type G-protein coupled receptor that may regulate dendritic morphology by organizing actin filaments. To begin to understand the function of C1QLs, we determined high-resolution crystal structures of the globular C1q-domains of C1QL1, C1QL2, and C1QL3. Each structure is a trimer, with each protomer forming a jelly-roll fold consisting of 10 beta strands. Moreover, C1QL trimers may assemble into higher-order oligomers similar to adiponectin and contain four Ca2+-binding sites along the trimeric symmetry axis, as well as additional surface Ca2+-binding sites. Mutation of Ca2+-coordinating residues along the trimeric symmetry axis lowered the Ca2+-binding affinity and protein stability. Our results reveal unique structural features of C1QLs among C1q/TNF superfamily proteins that may be associated with their specific brain functions.
Anatomical and Behavioral Investigation of C1ql3 in the Mouse Suprachiasmatic Nucleus
JOURNAL OF BIOLOGICAL RHYTHMS
Authors: Chew, Kylie S.; Fernandez, Diego C.; Hattar, Samer; Suedhof, Thomas C.; Martinelli, David C.
Abstract
Many biochemical, physiological, and behavioral processes such as glucose metabolism, body temperature, and sleep-wake cycles show regular daily rhythms. These circadian rhythms are adjusted to the environmental light-dark cycle by a central pacemaker located in the suprachiasmatic nucleus (SCN) in order for the processes to occur at appropriate times of day. Here, we investigated the expression and function of a synaptic organizing protein, C1QL3, in the SCN. We found that C1ql3 is robustly expressed in the SCN. C1ql3 knockout mice have a reduced density of excitatory synapses in the SCN. In addition, these mice exhibited less consolidated activity to the active portions of the day and period lengthening following a 15-minute phase-delaying light pulse. These data identify C1QL3 as a signaling molecule that is highly expressed in SCN neurons, where it contributes to the formation and/or maintenance of glutamatergic synapses and plays a role in circadian behaviors, which may include circadian aftereffects.