Bazinet RP，Layé S. Polyunsaturated fatty acids and their metabolites in brain function
and disease. Nat. Rev. Neurosci. 15: 771-785，2014.
Borgia A，Borgia MB，Bugge K，Kissling VM，Heidarsson PO，Fernandes CB，Sottini
A，Soranno A，Buholzer KJ，Nettels D，Kragelund BB，Best RB，Schuler BS. Extreme
disorder in an ultrahigh-affinity protein complex. Nature 555: 61-66，2018.
Brown DA. Lipid rafts，detergent-resistant membranes，and raft targeting signals.
Physiology 21: 430-439，2006.
Bruck S，Huber TB，Ingham RI，Kim K，Niederstrasser H，Allen PM，Pawson T，
Cooper JA. Shaw AS. Identification of a novel inhibitory actin-capping protein binding
motif in CD2-associated protein. J. Biol. Chem. 281: 19196-19203，2006.
Canton DA，Olsten ME，Niederstrasser H，Cooper Litchfield DW. The role of CKIP-1 in
cell morphology depends on its interaction with actin-capping protein. J. Biol. Chem.
281: 36347-36359，2006.
Darling AL，Zaslavsky BY，Uversky VN. Intrinsic disorder-base emergence in cellular
biology: Physiological and pathological liquid-liquid phase transitions in cells. Polymer
11: 990，2019.
Demarest SJ，Martinez-Yamout M，Chung J，Chen H，Xu W，Dyson HJ，Evans RM，
Wright PE. Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear
receptor coactivators. Nature 415: 549-553，2002.
Dyson HF and Wright PE. Inrinsically unstructured proteins and their functions. Nat.
Rev. Mol. Cell Biol. 6: 197-208，2005.
38
Epand EM，Braswell EH，Yip CM，Epand RF，Maekawa S. Quaternary structure of the
neuronal protein NAP-22 in aqueous solution. Biochim. Biophys. Acta 1650: 50-58，
2003.
Evers CE，McNeil H，Knebel A，Morrice N，Arthur SJ，Cuenda A，Cohen P. The
phosphorylation of CapZ-interacting protein（CapZIP） by stress-activated protein
kinases triggers its dissociation from CapZ. Biochem. J. 389: 127-135，2005.
Feng Z，Chen X，Wu X，Zhang M. Formation of biological condensates via phase
separation: Characteristics，analytical methods，and physiological implications. J. Biol.
Chem. 294: 14823-14835，2019.
Funatsu N，Kumanogoh H，Sokawa Y，Maekawa S. Identification of gelsolin as an actin
regulatory activity of a Triton insoluble low density fraction of bovine brain. Neurosci.
Res. 36: 311-317，2000.
Funatsu N，Miyata S，Kumanogoh H，Shigeta M，Hamada K，Endo Y，Sokawa Y，
Maekawa S. Characterization of a novel rat brain glycosylphosphatidylinositol-anchored
protein （Kilon）
，a member of the IgLON cell adhesion molecule family. J. Biol. Chem.
274: 8224-8230，1999.
Green LM，Wagner KJ，Campbell HA，Addison K，Roberts SG. Dynamic interaction
between WT1 and BASP1 in transcriptional regulation during differentiation. Nucleic.
Acid Res. 37: 431-440，2009.
Gotoh M，Sano-Maeda K，Murofushi，H，Murakami-Murofushi K. Protection of
Neuroblastoma Neuro2A cells from hypoxia-induced apoptosis by cyclic phosphatidic
acid（cPA）. Plos One 7: e51093，2012.
39
Hartl M，Puglisi K，Nist A，Raffeiner P，Bister K. The brain acid-soluble protein 1
（BASP1） interferes with the oncogenic capacity of MYC and its binding to calmodulin.
Mol. Oncol. 14: 625-644，2020.
Hartl M，Schneider R. A unique family of neuronal signaling proteins implicated in
oncogenesis and tumor suppression. Front. Oncol. 9: 289，2019.
Hutchings NJ，Clarkson N，Chalkley R，Barclay AN，Brown MH. Linking the T cell
surface protein CD2 to the actin-capping protein CapZ via CM5 and CIN85. J. Biol.
Chem. 278: 22396-22403，2003.
Iino S，Kobayashi S，Maekawa S. Immunohistochemical localization of a novel acidic
calmodulin-binding protein，NAP-22，in the rat brain. Neuroscience 91:1435-1444，
1999.
Ivanenkov VV，Dimlich RV，Jamicson GA，Jr. Interaction of S-100a0 protein with the
actin capping protein，CapZ: Characterization of a putative S100a0 binding site in CapZ
alpha-subunit. Biochim. Biophys. Res. Commun. 221: 46-50，1996.
Ivanenkov VV，Jamicson GA Jr，Gruenstein E，Dimlich RV. Characterization of S-100b
binding epitopes. Identification of a novel target，an actin capping protein，CapZ. J.
Biol. Chem. 270: 14651-14658，1995
Kim H-Y，Huang BX，Spector AA. Phosphatidylserine in the brain: Metabolism and
function. Prog. Lipid Res. 56: 1-18，2014.
40
Kim K，McCully ME，Bhattacharva N，Butler B，Sept B，Cooper JA. Structure/function
analysis of the interaction of phosphatidylinositol 4,5-bis phosphate with actin-capping
protein: implication for how capping protein binds the actin filaments. J. Biol. Chem.
282: 5871-4879，2007.
Kobayashi Y，da Silva R，Kumanogoh H，Miyata S，Sato C，Kitajima K，Nakamura S，
Morita M，Hayashi F，Maekawa S. Ganglioside contained in the neuronal tissueenriched protein of 22 kDa （NAP-22） fraction prepared from the detergent-resistant
membrane microdomain of rat brain inhibits the phosphatase activity of calcineurin. J.
Neurosci. Res. 93: 1462-1470，2015.
Korshunova I，Caroni P，Kolkova K，Berezin V，Bock E，Walmod，PS. Characterization
of BASP1-mediated neurite outgrowth. J. Neurosci. Res. 86: 2201-2213，2008.
Kriwacki RW，Hengst L，Tennant L，Reed SI，Wright PE. Structural studies of
p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates
binding diversity. Proc. Natl. Mol. Cell Biol. 6: 197-208，2005.
Kumanogoh H，Miyata S，Sokawa Y，Maekawa S. Biochemical and morphological
analysis on the localization of Rac1 in neurons. Neurosci. Res. 39: 189-196，2001.
Laux T，Fukami K，Thelen M，Golub T，Frey D，Caroni P. GAP43，MARCKS，and
CAP23 modulate PI（4,5）P2 at plasmalemmal rafts，and regulate cell cortex actin
dynamics through a common mechanism. J. Cell Biol. 149:1455-1472，2000.
Li P，Banjade S，Cheng H-C，Kim S，Chen B，Guo，L，Liaguno M，Hollingsworth JV，
King DS，Banani SF，Russo PS，Jiang Q-X，Nixon BT，Rosen. MK. Phase separation in
the assembly of multivalent signaling proteins. Nature 583: 336-340，2012.
41
Lingwood D，Simons K. Lipid rafts as a membrane-organizing principle. Science 327:
46-50，2010.
Maekawa S，Iino S，Miyata S. Molecular characterization of the detergent-insoluble
cholesterol-rich membrane microdomain（raft）of the central nervous system. Biochim.
Biophys. Acta 1610: 261-270，2003.
Maekawa S，Kobayashi M，Morita M，Suzaki T. Tight binding of NAP-22 with acidic
membrane lipids. Neurosci. Lett. 600: 244-248，2015.
Maekawa S，Kobayashi Y，Odagaki S-I，Makino M，Kumanogoh H，Nakamura S，
Morita M，Hayashi F. Interaction of NAP-22 with brain glutamic acid decarboxylase
（GAD）. Neurosci. Lett. 537: 50-54，2013.
Maekawa S，Kumanogoh H，Funatsu N，Takei N，Inoue K，Endo Y，Hamada K，
Sokawa Y.
Identification of NAP-22 and GAP- 43（neuromodulin） as major protein
components in a Triton insoluble low-BBadensity fraction of rat brain. Biochim. Biophys.
Acta 1323: 1-5，1997.
Maekawa S，Maekawa M，Hattori S，Nakamura S. Purification and molecular cloning of
a novel acidic calmodulin binding protein from rat brain. J. Biol. Chem. 268: 1370313709，1993.
Maekawa S，Matsuura Y and Nakamura S. Expression and myristoylation of NAP-22
using a Baculovirus transfer system. Biochim. Biophys. Acta 1218: 119-122，1994a.
Maekawa S，Murofushi H，Nakamura S. Inhibitory effect of calmodulin on
phosphorylation of NAP-22 with protein kinase C. J. Biol. Chem. 269: 19462-19465，
1994b.
42
Maekawa S，Sato C，Kitajima K，Funatsu N，Kumanogoh H，Sokawa Y. Cholesterol
dependent localization of NAP-22 on a neuronal membrane microdomain（raft）. J.
Biol. Chem. 274: 21369-21374，1999.
Maekawa S，Toriyama M，Hisanaga S-I，Yonezawa N，Endo S，Hirokawa N，Sakai，H.
Purification and characterization of a Ca2+-dependent actin filament severing protein
from bovine adrenal medulla. J. Biol. Chem. 265: 7458-7465，1989.
Marsh LA，Carrera S，Shandilya J，Heesom J，Davidson AD，Medler K，Robbertis S
GE. BASP1 interacts with oestrogen receptorαand modifies the tamoxifen response. Cell
Death Dis. 8: e2771，2017.
Maruyama Y，Ueno S，Morita M，Hayashi F，Maekawa.，S. Inhibitory effect of several
sphingolipid metabolites on calcineurin. Neurosci. Lett. 673: 132-135，2018.
Matsuura D，Taguchi K，Yagisawa H，Maekawa S. Lipid components in the detergentresistant membrane microdomain（DRM）obtained from the synaptic plasma
membrane of rat brain. Neurosci. Lett. 423: 158-161，2007.
Melasco M，O’Sullivan C，Sheridan GK. Lysophosphatidic acid receptors （LPARs）:
Potential targets for the treatment of neuropathic pain. Neuropharmacology 11: 608617，2017.
Mittag T，Orlicky S，Choy WY，Tang X，Lin H，Sicheri F，Kay LE，Tyers M，FormanKay JD. Dynamic equilibrium engagement of a polyvalent ligand with a single-site
receptor. Proc. Natl. Acad. Sci. U. S. A. 105: 17772-17777，2008.
43
Mosevitsky MI. Nerve ending “signal” proteins GAP-43，MARCKS and BASP1. Int. Rev.
Cytol. 245: 245-325，2005.
Nielsen MM，Lambertsen KL，Clausen BH，Meyer M，Bhandari DR，Larsen，ST，
Poulsen SS，Spengler，B，Janfelt C，Hansen H. Mass spectrometry imaging of
biomarker lipids for phagocytosis and signaling during cerebral ischemia. Sci. Rep. 6:
39571，2016.
Odagaki S-I，Kumanogoh H，Nakamura S，Maekawa S. Biochemical Interaction of an
Actin-Capping Protein，CapZ，with NAP-22. J. Neurosci. Res. 87: 1980-1985，2009.
Odagaki S-I，Maekawa S，Hayashi F，Suzaki T，Morigaki K. The effects of
phospholipids and fatty acids on the oligomer formation of NAP-22. Neurosci. Lett. 736:
135288，2020.
Ostroumova OS，Schagina LV，Mosevisky，MI，Zakharov VV. Ion channel activity of
brain abundant protein BASP1 in planar lipid bilayers. FEBS J. 278: 461-469，2016.
Raghupathy R，Anilkmar AA，Polley A，Singh PP，Yadaf M，Johnson C，Suryawanshi
S，Saikam V，Sawant SD，Panda A，Guo Z，Vishwakarma RA，Rao M，Mayor S.
Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins. Cell
161: 581-594，2015.
Ryan V，Fawzi NL. Physiological，pathlogical，and targetable membraneless organelles
in neurons. Trends Neurosci. 42: 693-708，2019.
Salauen C，James DJ，Chamberlain LH. Lipid rafts and the regulation of exocytosis.
Traffic 5: 255-264，2004.
44
Sanchez-Nino D，Sanz AB，Lorz C，Grinke A，Rastaldi MP，Nair V，Egido J，RuizOrtega M，Kretzler，M，Oritz A. BASP1 promotes apoptosis in diabetic nephropathy. J.
Am. Soc. Nephrol. 21: 610-621，2010.
Schafer DA，Jenning DJ，Cooper JA. Dynamics of capping protein and actin assembly in
vitro: uncapping barbed end by polyphosphoinositides. J. Cell Biol. 135: 255-264，
1996.
Simons K，Toomre D. Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1: 3139，2000.
Snead W，Gladfelter AS. The control centers of biomolecular phase separation: How
membrane surfaces，PTMs，and active processes regulate condensation. Mol. Cell 76:
295-305，2019.
Sugase K，Dyson HJ，Wright PE. Mechanism of coupled folding and binding of an
intrinsically disordered protein. Nature 447: 1021-1025，2007.
Taguchi K，Kumanogoh H，Nakamura S，Maekawa S. Localization of phospholipase C 1
on the detergent-resistant membrane microdomain prepared from the synaptic plasma
membrane fraction of rat brain. J. Neurosci. Res. 85: 1364-1371，2007.
Takaichi R，Odagaki S-I，Kumagnogoh H，Nakamura S，Morita M，Maekawa S.
Inhibitory effect of NAP-22 on the phosphatase activity of synaptojanin-1. J. Neurosci.
Res. 70: 21-27，2012.
45
Taoka M，Ichimura T，Wakamiya-Tsuruta A，Kubota Y，Araki T，Obinata T，Isobe T.
V-1，a protein expressed transiently during murine cerebellar development，regulates
actin polymerization via interaction with capping protein. J. Biol. Chem. 278: 58645870，2003.
Terashita A，Funatsu N，Umeda M，Shimada Y，Ohno-Iwashita Y，Epand RM，
Maekawa S. The lipid binding activity of a neuron specific protein NAP-22 studied in vivo
and in vitro. J. Neurosci. Res. 70: 172-179，2002.
Ueno S，Miyoshi，H，Maruyama Y，Morita，M，Maekawa S. Interaction of dynamin I
with NAP-22，a neuronal protein enriched in the presynaptic region. Neurosci. Lett.
675: 59-63，2018.
Uruno T，Remmer K，Hammer JA，3rd. CARMIL，is a potent capping protein
antagonist: identification of a conserved CARMIL domain that inhibits the activity of
capping protein and uncaps capped actin filaments. J. Biol. Chem. 281: 10635-10650，
2006.
Yamamoto Y，Sokawa Y，Maekawa S. Biochemical evidence for the presence of NAP22，a novel acidic calmodulin binding protein，in the synaptic vesicles of rat brain.
Neurosci. Lett. 224: 127- 130，1997.
Yoshinaka K，Kumanogoh H，Nakamura S，Maekawa S. Identification of V-ATPase
as a major component in the raft fraction prepared from the synaptic plasma
membrane and the synaptic vesicle of rat brain. Neurosci. Lett. 363 168-172，2004.
Yung YC，Stoddard NC，Mirendil H，Chun J. Lysophosphatidic acid signaling in the
nervous system. Neuron 18: 669-682，2015.
46
Zakharov VV，Mosevitsky MI. Oligomeric structure of brain abundant proteins GAP-43
and BASP1，J. Struct. Biol. 170: 470-483，2010.
謝辞
第 1 章で用いた，CapZ 発現プラスミドは，大日方博士（千葉大学）
，前田博士・武田博士
（ERATO）
（所属は当時のもの）よりご供与いただきました。タンパク質の質量分析は，中村俊
部長，熊ノ郷 晴子博士（国立精神・神経センター，神経研）
（当時）にお世話になりました。
第 2 章の電子顕微鏡の試料作成と観察，結果の検討では，洲崎敏伸先生（神戸大学理学研究
科）に何度も長時間，ご指導いただきました。伏して感謝を申し上げます。
47
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