mlcD encodes the myosin-ID light chain (UniProt Q7Z2B8), a 147 amino acid calmodulin-like protein that serves as the dedicated light chain for the class I myosin MyoD (Myo1D) in Dictyostelium discoideum.
MlcD was discovered as a novel 16 kDa light chain that co-purifies with MyoD. Two copies of MlcD associate with each MyoD heavy chain PMID:12826013. The protein has four EF-hand motifs but only weak calcium binding PMID:12826013. Critically, MlcD binds calcium only at low affinity PMID:12826013. This low affinity means it is not a physiological calcium sensor PMID:12826013. MlcD binding to MyoD is calcium-insensitive PMID:12826013. MlcD is specific to MyoD and does not interact with MyoB or MyoC PMID:12826013. The protein is localized to the cytoplasm PMID:12826013.
The related light chain MlcB for MyoB was characterized and compared with MlcD. MlcD was confirmed as specifically associated with MyoD PMID:16415352. This work established that each long-tailed class I myosin in Dictyostelium has a distinct light chain.
A comprehensive study established the complete light chain complement: MyoB-MlcB, MyoC-MlcC, MyoD-MlcD for the long-tailed myosin I isoforms, while short-tailed MyoA and MyoE use calmodulin PMID:21671662. The diversity in light chain composition contributes to distinct cellular functions PMID:21671662.
MlcD localizes with MyoD (Myo1D) to macropinocytic structures and actin waves. Myo1D localizes to macropinocytic cups and the PIP3-enriched region inside actin waves PMID:31774725. This is distinct from Myo1B, which localizes to the actin wave itself PMID:31774725. Myo1D is found in pinocytic protrusions and cups, and freshly internalized vesicles PMID:31774725.
MlcD is a structural/regulatory light chain subunit of the myosin I complex containing MyoD (Myo1D). It is a calmodulin-related protein with degenerate EF-hands that retains only low-affinity calcium binding. Its primary molecular function is binding the MyoD heavy chain at IQ motifs in a calcium-insensitive manner, serving as an essential structural subunit of the Myo1D motor complex. Through this association, MlcD participates in macropinocytosis-related membrane dynamics and actin wave organization.