ReviewMultiple faces of protein interacting with C kinase 1 (PICK1): Structure, function, and diseases
Section snippets
Structure
Protein interacting with C-kinase 1 (PICK1) was cloned as a protein kinase C-α (PKCα)-binding protein, which is expressed in multiple tissues and organs, mostly abundant in the brain and testis (Staudinger et al., 1995, Staudinger et al., 1997, Wang et al., 2003, Wang et al., 2007). The expression of PICK1 starts as early as embryonic 15 days, and continues to increase until two weeks after birth (Xia et al., 1999). The high evolutionary conservatism of PICK1 from non-vertebrate animals to
Rab39B
It is recently found that PICK1 is a downstream effector of Rab39B, a small GTPase, suggesting new roles of PICK1 in Rab39B-related disorders (Mignogna et al., 2015). Mutation of Rab39B causes intellectual disability in autism spectrum disorder and epilepsy. Rab39B-PICK1 complex controls GluA2 trafficking from endoplasmic reticulum to Golgi apparatus and the surface expression of GluA2. The down-regulation of Rab39B skews AMPAR composition towards non GluA2-containing Ca2+-permeable forms and
Chronic pain
PICK1 affects pain in CNS mainly through acid-sensing ion channel (ASIC) and AMPAR. PICK1 co-expresses with ASIC1a and ASIC2a in cortical and hippocampal CA3 pyramidal cells, and Purkinje neurons. PICK1 enhances ASIC2a current by phosphorylation and increases open probability of ASIC channels (Baron et al., 2002). PICK1 also plays key roles in neuropathic pain by interacting with GluA2 and thereby affects hyperalgesia in the constriction injury of sciatic nerve (Atianjoh et al., 2010; Garry
Fertility
PICK1 is abundantly expressed in testis. Hence, the function of PICK1 in testis has been well studied, mainly focusing on male infertility disorders. Data derived from PICK1-knockout mice or patients carrying PICK1 mutation show that the dysregulation of PICK1 results in globozoospermia. In human, an autosomal recessive genetic mutation (G198A) in exon 13 of PICK1 gene is responsible for globozoospermia, as shown by a complete lack of acrosome in sperm cells (Liu et al., 2010). Restoring PICK1
Conclusions
To date, more than 40 proteins are found to bind to PICK1. The unique structure of PICK1 enables it to play important roles in many aspects of cell structure and function, as shown by the schematic illustration summarizing major proteins interacting with PICK1 (Fig. 1). PICK1 is involved in not only intracellular processes such as trafficking and activity, but also in neurological and non-neurological diseases. Although underlying mechanisms for PICK1 functions in these diseases are unclear,
Acknowledgment
This work was supported by National Natural Science Foundation of China (31460257, 31471024, and 31271148). We are grateful for helpful advice from members of Shen laboratory.
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Electroacupuncture prevents LPS- induced neuroinflammation via upregulation of PICK-TLR4 complexes in the microglia of hippocampus
2021, Brain Research BulletinCitation Excerpt :The BAR domain of PICK1 binds to lipid molecules, mainly phosphoinositides. Because its PDZ domain interacts with membrane proteins and its BAR domain binds to lipids, PICK1's unique structure enables it to couple membrane proteins with protein transport mechanisms (Li et al., 2016). Studies have shown that EA can relieve septic encephalopathy by inhibiting microglial activity (Chen et al., 2016).
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