Fig. 8. Proposed scheme for DIF signaling pathways in D. discoideum.

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Fig. 8. Proposed scheme for DIF signaling pathways in D. discoideum. Proposed scheme for DIF signaling pathways in D. discoideum. (A) Hypothetical receptors for DIF-1 and DIF-2 control cell differentiation and chemotaxis. We assume that DIF-1 has two receptors: DR1-D (DR-1 in Kuwayama et al., 2011) and DR1-C (DR-2 in Kuwayama et al., 2011); DIF-2 has one receptor, DR2-C (DR-3 in Kuwayama et al., 2011). We hypothesize that (1) DIF-1 induces stalk cell differentiation via DR1-D (DIF-1 receptor responsible for induction of cell differentiation) and an increase in cytosolic calcium and proton concentrations (Kubohara and Okamoto, 1994; Kubohara et al., 2007); (2) DIF-1 suppresses chemotactic cell movement in shallow cAMP gradients via DR1-C (DIF-1 receptor responsible for modulation of chemotaxis) and the GbpB-dependent pathway; and (3) DIF-2 promotes chemotactic cell movement in shallow cAMP gradients via DR2-C (DIF-2 receptor responsible for modulation of chemotaxis) and the Dictyostelium histidine kinase C (DhkC)-RegA-dependent pathway (Kuwayama and Kubohara, 2016, 2009; Kuwayama et al., 2011). DhkC might function as DR2-C (Kuwayama and Kubohara, 2016). DIF-2 would also induce stalk cell differentiation via DR1-D (dotted arrow) due to its structural similarity to DIF-1. (B) Newly proposed scheme for chemotaxis modulation by DIF-1. DIF-1 localizes to mitochondria and suppresses chemotaxis in shallow cAMP gradients. Because CCCP and DNP, similar to DIF-1, suppress chemotaxis in shallow cAMP gradients, DIF-1 might suppress chemotactic cell movement via mitochondria and the GbpB-dependent pathway; DR1-C might reside in mitochondria. (C) Cellular localization of DIF-1 during early cell differentiation. In vegetative cells, DIF-1 penetrates the cell membrane but is continuously pumped out of the cells; in differentiating (aggregating) cells, DIF-1 is retained in some cells because of inactivation or disappearance of the pump. It is localized to mitochondria and promotes stalk cell differentiation. Yuzuru Kubohara et al. Biology Open 2017;6:741-751 © 2017. Published by The Company of Biologists Ltd